Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Continue reading...

The Revised Authoritative Guide To Vaccine Legal Exemptions Summary


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Vaccinesbased immunotherapy

GVAX (CGI940 CG8711 is a cellular vaccine composed of two allogeneic prostate cancer cell lines (LNCaP and PC-3 that is genetically modified to secrete GM-CSF 69 . This vaccine showed clinical benefit with limited toxicity in phase I and II trials 70, 71 . However, the two phase III trials (VITAL-1 and VITAL-2 evaluated GVAX against docetaxel plus pre-dnisone in nai've CRPC and both were closed prematurely 70 . The VITAL-1 study was closed when the unplanned futility analysis revealed a < 30 chance of meeting its predefined primary endpoint of OS improvement and the VITAL-2 terminated when an interim analysis revealed more deaths in the GVAX arm than in the control 71 . PROSTVAC-VF is a cancer vaccine consisting of a recombinant vaccinia vector as a priming immunization with subsequent multiple booster vaccinations, using a recombinant fowlpox vector. This agent presented in the context of 3 costimulatory molecules (ICAM-1, BLA-7, and LFA-3 which, when taken together, demonstrate an...

Biological and other realities of influenza and impact on public health and vaccine production

Public health and other Impact on vaccine Some regulatory agencies require small clinical trials before approval to market after a strain has changed in the influenza vaccine Annual revaccination needed shortly before influenza season. Vaccine required in NH before Nov December and in SH before April May Vaccine must be produced with currently circulating or emerging dominant virus to maintain high vaccine efficacy Clinical trials are to be executed during the narrow window between availability of first vaccine doses and annual immunization campaigns Vaccine production must start in Ian and Sep to ensure supply ahead of the NH and SH outbreaks, respectively High-growth reassortants derived from the dominating wild viruses are to be available 1 month before production begins (to allow for seed virus preparation) Standardizing reagents (serum) must always be updated when strains change. Reagents are needed early after beginning of production to measure strain yield and to calibrate...

Dna Vaccines For Infectious Diseases And Cancer

DNA Vaccines Against HIV-1 The human immunodeficiency virus-1 (HIV-1) is a retrovirus, which preferentially infects and kills CD4+ T cells and macrophages, ultimately resulting in immune system failure andmultipathogen infections. Recent breakthroughs in combination therapy using 3 or more different antiretroviral agents have generated optimism regarding the ability to control viral replication in vivo (21). However, this therapeutic regimen is costly, and it is too early to tell whether this approach can eradicate established infection (21,22). The costs and the stringent administration regimen requirements of these pharmaceutical agents make it clear that these drugs will only be effectively used in a limited part of the world population. Therefore, to address the worldwide problem of HIV-1 infection, there remains a need for a prophylactic vaccination strategy designed to control the epidemic through mass immunization campaigns (23). One of the major obstacles in the development...

National Childhood Vaccine Injury Act of 1986

A vaccine safety and compensation system established by Congress in 1986 to create a no-fault compensation alternative to suing vaccine manufacturers and providers for citizens injured or killed by vaccines. The act also created safety provisions to help educate the public about vaccine benefits and risks, and to require doctors to report adverse events after vaccination as well as keep records on vaccines administered and health problems which occur following vaccination. Finally, the act also created incentives for the production of safer vaccines. For any injuries or deaths before October 1, 1988 (no matter how long ago the injury occurred), a citizen may choose to pursue a lawsuit. For injuries or deaths occurring after that date, a citizen is required to apply for federal compensation before pursuing a lawsuit. The government will offer to pay up to 250,000 for a vaccine-associated death, or will offer to pay for all past and future unreimbursed medical expenses, custodial and...

National Vaccine Injury Compensation Program

The NATIONAL CHILDHOOD VACCINE INJURY ACT of 1986 (PL 99-660). The program is designed to ensure an adequate supply of vaccines, stabilize vaccine costs, and maintain an efficient way to help children injured by childhood vaccines. The program, which went into effect October 1, 1988, is a no-fault alternative to the traditional tort system for resolving vaccine injury claims. Since its inception, the Vaccine Injury Compensation Program (VICP) has helped stabilize the U.S. vaccine market by providing liability protection to both vaccine companies and health-care providers, by encouraging research and development of new and safer vaccines, and by allowing a quicker and less adversarial alternative to lawsuits. The VICP covers all vaccines recommended by the Centers for Disease Control and Prevention for routine administration to children In the early 1980s reports of harmful side effects after the DTP (diphtheria, tetanus, pertussis) vaccine posed major liability concerns for vaccine...

The Dream of a Vaccine

Despite all the research that has gone into developing treatments for HIV and AIDS, many experts believe that prevention of HIV infection in the first place remains the best hope for halting the epidemic. To that end, experts believe that an HIV vaccine is required since, historically, only vaccines have been able to eradicate a given disease. As Sam Avrett, the associate scientific director of the International AIDS Vaccine Initiative (IAVI), explained Vaccine research is critical because a vaccine is one of the best foreseeable ways to control the AIDS epidemic, both in the U.S. and around the world. Anyone who has worked in HIV prevention knows that, while behavioral change and condoms and clean needles go a long way toward preventing HIV, staying uninfected is hard. . . . Although behavior change can do a lot, it is just not realistic to expect individual behavior change, by itself, to control this epidemic.39 Some experts hope that not only might HIV vaccines prevent infection,...

Pneumococcal conjugate vaccine PCV A new

Vaccine approved in 2000 to prevent invasive pneumococcal diseases in infants and toddlers, diseases that can cause brain damage and, in rare cases, death. The pneumococcal conjugate vaccine (PCV) is not indicated for use in adults or as a substitute for other approved pneumococcal polysac-charide vaccines approved for high-risk children over age two. The previous pneumococcal vaccine (PPV) was not recommended for use in children under age two, who contract the most serious infections from this bacteria. The new PCV vaccine (Prevnar) protects against the organism Streptococcus pneumoniae (also known as pneumococcus), the leading cause of pneumonia, sinusitis, ear infection, and meningitis. It has been added to the recommended schedule of childhood immunizations. It is given to infants as a series of four inoculations administered at age two, four, six, and 12 to 15 months of age. If a child cannot begin the vaccine at two months, parents should discuss alternative schedules with their...

Recommendations for Vaccinations in Children with Rheumatic Disease

All vaccines recommended may be given, but avoid rubella if the child has a positive Most routine vaccinations are okay, but avoid rubella if the child has a positive titer. Do not give any live-virus vaccines (e.g., chicken pox herpes zoster and smallpox), as there is risk of disease and Reye's syndrome. Child with arthritis who is on immunosuppressive medications (corticosteroids, etanercept, infliximab, anakinra, adalimumab) or cytotoxics (methotrexate, mycophenolate mofetil, cyclophosphamide, azathioprine) Do not give the child any vaccinations. However, there are data suggesting that pneumococcal vaccine should be given if it hasn't already been. No live-virus vaccinations should be given to siblings or household contacts. Child with active arthritis within the past six months (no matter what the medications) No vaccinations should be given to the child (note that not all doctors agree on this). This has to be reviewed on a case-by-case basis when issues such as college dormitory...

Consequences of Malaria Vaccination

The data so far indicate that in malaria the common factor underlying the V-T-P relationships is asexual parasite density. We reasoned, therefore, that any control measures that brought about a reduction in asexual parasite densities, such as an asexual stage, anti-replication vaccine, would bring about evolution for increased intrinsic virulence because of its consequences to transmissibility, persistence and host mortality (Gandon et al., 2001). If this evolution were to happen, the unprotected (e.g. unvaccinated) people in the population would then be exposed to a more virulent parasite and their risk of death would be higher than before. On the other hand, it might be argued, the vaccine, if used widely, would protect many more people from disease so that the population-wide reduction in mortality may well outweigh the increased mortality among the unvaccinated few. Thus, as is often the case in vaccination programmes, even without evolution, the benefits to the majority of the...

What is the vaccine for MS

There seems to be a great deal of confusion in the minds of many MS patients and their families about a vaccine for MS. Some seem to think of any injectable drug as a vaccine, but this is not a correct concept. All of the medications currently approved by the FDA for chronic (long-term) use in MS are drugs but are not considered to be vaccines, although their use is to prevent periods of ill health. Interferon-beta-lb (Betaseron) and interferon-beta-la (Avonex and Rebif) and glatiramer acetate (Copaxone) are injectable drugs but are not vaccines. In contrast, a vaccine, which is generally injected, stimulates the immune system, resulting in antibody formation or a direct effect of lymphocytes against proteins or cells that have specific proteins on their surface. Several vaccines against cells in the immune system have been used in research trials.

Is there going to be a vaccine for MS

There is ongoing research into T-cell vaccines for MS. The original experiments in Europe attracted great interest. They involved injecting crude preparations of blood lymphocytes into patients in an attempt to eliminate or reduce the number of activated lymphocytes in MS patients. Ongoing studies involve a more sophisticated selection of cells to be targeted for removal by immune action. They appear to be tolerable and effective to a degree. They do not result in a long-lasting benefit. Other stalled studies attempted to induce immune tolerance without provoking a direct attack on existing cells only preliminary data on their safety have been published. No studies of this third generation type of vaccine are continuing.

Criteria to be fulfilled by influenza vaccine candidate viruses

Sucrose Gradient Virus

Differ from the vaccine virus strains as characterized by the HI test supported by clinical and epidemiological information and (a) genetic characterization and (b) serological tests with sera from subjects immunized with current seasonal influenza vaccine Suitable for vaccine preparation To comply with regulatory requirements, vaccine companies require virus isolates that (a) are antigenically and genetically similar to those identified by WHO as becoming dominant (b) have a known passage history isolated on approved egg substrates (With more influenza vaccine producers switching over to cell-culture production, standards are also developed by regulatory agencies for viruses isolated in cell culture.) (c) have acceptable growth characteristics (grow well in hens eggs) 1. Antigenically (ignificantly different from the current vaccine virus strains 3. Suitable for vaccine strain preparation To this end, the viruses from the National Influenza Centers are tested for how well their...

Vaccine Injury Compensation Program A

Special program, passed by Congress in 1986, that provides compensation for children who have adverse results after receiving vaccines. All claims are reviewed by medical staff, and awards are decided by a group of attorneys of the U.S. claims court. The program is paid for by a surtax on all vaccines, and it applies to DPT, MMR, OPV, and Td, vaccines. To report an adverse event after a vaccine, call the doctor where your child received the shot to report any reactions. Give complete information about what happened and when it occurred. Your doctor should report any unusual or serious reactions to the Vaccine Adverse Events Reporting System at (800) 822-7967. In Canada, the province of Quebec is the only one with a vaccine injury plan. vaccinia A viral cattle disease (cowpox) inoculated in humans to produce an antibody against SMALLPOX. Vaccinia is the source of the word vaccine.

Vaccines against pancreatic tumour antigens

To develop the ideal vaccine for pancreatic cancer, the following wish list would probably need to be fulfilled. First, specific cell-surface proteins must be identified that are that are crucial in the cancer growth or progression pathway and are unique to pancreatic cancer tumours. Second, these tumour-exclusive proteins should be shown to elicit a vigorous tumour-protein-specific immune response. Third, the best carrier to deliver the appropriate immunogenic tumour proteins should be identified. Fourth, molecules that are immune stimulatory as well as molecules that can abrogate the natural immune-inhibition signalling that is seen in pancreatic cancer should be identified to enhance the immune response. Fifth, additional synergistic immune help should be identified (for example, antibodies or ex vivo tumour-reactive T cells). Several proteins, such as carcinoembryonic antigen (CEA), mutated KRAS, mucin-1 (MUC1) and gastrin, have in fact been identified to be specifically...

Vaccine Driven Virulence Evolution in Other Diseases

Are there any examples where vaccines have driven the pathogen towards higher virulence Vaccines against smallpox, measles and polio have been remarkably successful. Among these, only polio virulence has been shown to increase in response to vaccination pressure (Kew et al., 2002) in this case it was the attenuated vaccine strain that reverted to virulence and transmissibility rather than the wild-type strain changing in response to vaccination. In the case of measles and smallpox, the vaccine induces near-sterilizing immunity, and so it is therefore not surprising that evolution seems not to have occurred. On the other hand, for diseases where vaccines are more imperfect (i.e. less effective), changes in pathogen virulence following vaccination have been documented, but not always in the direction we predict here, e.g. diphtheria, pneumo-coccal disease and whooping cough (pertussis). Such cases highlight an important distinction between the type of virulence evolution we have been...

Vaccine delivery and future research

One of the major goals of future research into mucosal immune responses is the development of oral vaccines that are capable of stimulating lasting systemic immunity as well as local mucosal immune responses. Such vaccines must stimulate active immunity rather than immunological tolerance and the immune responses induced must be appropriate for control of the target pathogen. Currently a limited number of oral vaccines are approved for human use these include the oral polio vaccine, a live-attenuated typhoid vaccine and an oral adenovirus vaccine (Brandtzaeg, 2003). A live-attenuated rotavirus vaccine was recently withdrawn, owing to serious adverse reactions to the vaccine. However, new rotavirus vaccines are currently in the later stages of development (Glass et al., 2005). An objective of research into mucosal vaccines is the creation of a multivalent vaccine that can offer protection against a number of food- and waterborne pathogens (Walker, 2005). Organisms such as V. cholerae,...

Importance Of Vaccines

Historical Importance of Vaccines Vaccination is a deliberate introduction of materials in humans to elicit immune protection against diseases (1). For example, some Indian Buddhists drank snake venom to protect themselves from snake bites (1). During the 9th century in China, The Correct Treatment of Small Pox was written by a Buddhist nun. The manuscript recommended a mixture of ground dried smallpox scabs and herb to be blown into the nostrils of children. Even with such a long history, immunization was not widely used until Edward Jenner deliberately injected cowpox virus into humans to protect them from ravages of smallpox. Since that time, wide use of vaccines against pathogenic microorganisms has become the most important advance in the history of medicine. Vaccines have not only provided protection from smallpox, but also from poliomyelitis, measles, mumps, rubella, yellow fever, pertussis (whooping cough), hepatitis A, hepatitis B, and varicella, as well as others. These...

Ad Vaccine Carriers

The strong humoral and cellular immune response to the expressed transgene suggests that adenovirus vectors may be effective as vaccines for infectious diseases and cancer. It is possible that there is an inflammatory response to Ad capsids or to residual Ad gene expression that enhances the immune response over that obtained by expression from a plasmid vector. Alternatively, the ability of Ad to directly infect dendritic cells in vivo (78,149) and express the antigen gene may result in antigen presentation by the class I pathway. Examples of exploiting the cellular antitransgene response include eliciting a cellular immune response to tumor antigens as discussed earlier. This property may also be useful in elimination of virus-infected cells (150-152) or malaria (153). It is clear that antigens expressed by Ad also elicit a strong humoral immunity that can be used to block initial infection by viruses (154,155). In the context that most humans have been infected by wild-type...


Active immunization is provided by a vaccination that stimulates the immune system to make protective antibodies that protect you for life. The chicken pox vaccine Varivax is made from a The development of a vaccine against the disease has been studied and used in clinical trials with children and adults in the United States since the early 1980s it has been used in Japan for some time. It protects 70 to 90 percent of children but does not work well on adults. In March 1995 the U.S. Food and Drug Administration licensed the vaccine for general use the American Academy of Pediatrics has recommended the vaccine for all children and teenagers. Children younger than 12 require one dose children 13 and over require two shots four to eight weeks apart. Not all physicians agree on the benefits of the vaccine for healthy children, however. While proponents of the vaccine point out that suffering children and parents' considerable lost work time are good reasons to use the vaccine, some...


It suggests a possible role for these vectors as vehicles for prophylactic or therapeutic vaccines. For example, one study demonstrated that a recombinant AAV vector expressing a secreted HSV-2 gB led to the activation of gB-specific CTL, which were most likely activated via cross-presentation of the secreted protein by DC (195). In contrast, mice injected intramuscularly with an AAV vector expressing ovalbumin developed a robust humoral response to the transgene product but only a minimal ovalbumin-specific CTL response (199). In rhesus macaques, a single-dose, intramuscular administration of an AAV vector expressing the simian immunodeficiency virus (SIV) major structural genes resulted in long-term CD8 +, antigen-specific CTL responses against multiple SIV protein epitopes that were similar to responses observed in monkeys directly infected with pathogenic SIV. Neutralizing antibody responses were also robust and persisted for more than 1 year. More recent studies have begun to...

Genes and vaccines

To take another example, vaccines against disease are traditionally prepared from killed or disarmed pathogens (disease-causing microbes). They are effective in the vast majority of people, but a small percentage of the population have allergic reactions to vaccines. There is also a very small risk of vaccine organisms reactivating to their former pathogenic state. Genetically engineered vaccines are safer because they contain no living organisms, only the proteins that stimulate the body to develop immunity (Figure 3.3). Engineered vaccine A safe vaccine against viral disease can be produced by engineering the gene for the viruses' protein coat into bacteria. The bacteria manufacture the viral coat protein, which is then injected to stimulate the body to make antibodies against the virus. vaccine vaccine Vaccines are the second-largest category of over 200 drugs now being produced by American pharmaceutical companies using biotechnology. Other products include hormones, interferons,...

Polio vaccine

Until recently, the live oral polio vaccine (OPV) had been recommended for most children because while both vaccines provide immunity to polio, OPV was better at keeping the disease from spreading to other people. However, for a few people (about one in 2.4 million), OPV actually causes polio. Since there is now virtually no chance of getting polio in the United States, experts decided that using oral polio vaccine is no longer worth the chance of infecting five to 15 American children each year. The killed virus polio shot (IPV) never causes polio and is not known to cause any side effects other than minor local pain and redness.

Routine Vaccinations

The most important thing to understand about immunizations is that they have saved millions of lives. Routine vaccination against smallpox eliminated a terrible and often fatal disease from the world. Although it may take a full generation, routine immunization against hepatitis B will also save hundreds of thousands of lives. You will find it nearly impossible to locate a young American doctor with experience treating polio, measles, mumps, rubella, or their complications because routine vaccination has made these diseases very rare. At present, every American child is routinely vaccinated against polio, tetanus, measles, mumps, rubella, pertussis (whooping cough), and hepatitis B. To meet the current recommendations of the American Academy of Pediatrics, children receive at least fifteen vaccinations during the first three years of life. Pauciarticular-onset juvenile arthritis frequently starts in young children in this age group, so chances are that children develop the disease...

Other Vaccines

It is now recommended by the American Academy of Pediatrics that young children receive the pneumococcal vaccine (Pneumovax) vaccination early in life. It prevents many types of serious pneumonia and other infections caused by the same family of bacteria. Most older children have not gotten it. It should be given to children if you think you are going to put them on immunosuppressive medications, but it must be given before you start the immunosuppressive medication for it to be most effective. There is evidence that it still has some benefit even if the children are on immunosuppressive medicine. This is safe because it is not a live vaccine. Meningococcal vaccine. The meningococcal vaccine, which protects against meningitis, is frequently recommended for college freshman and increasingly for even younger children. Human papillomavirus (HPV). The newly introduced HPV vaccine (Gardasil) is being recommended for girls to reduce the risk of cervical cancer. There...

DNA vaccines

DNA vaccines are based on the expression in 'vaccinated' hosts of cDNA encoding protein antigens (viz. viral coat proteins) that have been cloned into plasmid vectors carrying transcription and translation signal sequences utilized by the host's cellular molecular machinery. Specific genetic elements can be engineered into the vector to permit replication in target cells.145,246 Expression of the protein antigens generates both humoral (antibodies) and cell-mediated (cytotoxic T lymphocyte or CTL) responses to the antigen, conferring protection against subsequent infection by the same or related pathogen. The advantage of DNA vaccines over inactivated or live attenuated pathogens is that large quantities of highly purified pathogens are not needed, and that both CTL and antibody responses are induced, which are crucial for establishing protective (i.e. relevant) immunity. The advantage of DNA vaccines over immunization with live attenuated pathogens, which also elicit a CTL response,...

Enhancement of Animal Host Response

Vaccination of animals, particularly when combined with other measures implemented further along the food chain, is considered as a promising strategy for foodborne pathogen reduction. For example, in pigs and cattle, vaccines against Salmonella strains causing disease have been successfully used (House et al., 2001) and vaccination of poultry against Salmonella contributed to significant reduction of the pathogen in poultry meat in the UK. Nevertheless, for other pathogens, such as E. coli O157 or Campylobacter, vaccines are being researched but effective ones are not yet commercially available.

Many battles won but the war goes onthe evolution of antimicrobial resistance

More than 6 decades following the availability of penicillin, and in the wake of the eradication of naturally occurring smallpox by global vaccination and dramatic decreases in infections like diphtheria, tetanus, and poliomyelitis by their respective vaccines, infectious diseases remain a major cause of morbidity and mortality in the world. Although many new drugs have been discovered, so have many new infectious agents. However, the biggest hurdle in the path to victory has been the development of resistance to antibiotics by most types of bacteria 31 . Given that antibiotics are mediating a war between the human species and thousands of bacterial species, the counterstrike was expected and anticipated at a pace determined by the genetic constitution of various bacteria. What was not a part of the long-range plan was the widespread use, abuse, and misuse of antibiotics prevalent in various forms in different parts of the world.

The Future Of Multiple Sclerosis Treatments

As more is understood about the natural mechanisms for establishing and maintaining this tolerance, new drugs will be designed to treat MS. Our knowledge of immune regulation is built partly on the tremendous strides made in this century in augmenting with vaccines the immune system's ability to fight infectious diseases that once were uniformly fatal or disabling. Strategies for treating MS and other autoimmune diseases, and for tolerating transplanted organs, may include vaccines to train the immune system not to react.

Firstgeneration Adenoviral Vectors

Proliferating cell types from various species to direct highlevel gene expression. Consequently, Ad vectors are extensively used as potential recombinant viral vaccines, for highlevel protein production in cultured cells and for gene therapy (for reviews, see 11-15). First-generation Ad vectors (FGAds) typically have foreign DNA inserted in place of early region 1 (E1). El-deleted vectors are replication deficient and are propagated in E1-complementing cells such as 293 (16). Typically, FGAds also have a deletion in the nonessential E3 region to maximize cloning capacity. The fundamental principle underlying all current methods of constructing FGAds is based on the discovery that up to 10 of Ad viral DNA molecules become circularized following infection of mammalian cells (17). This permitted cloning of the entire Ad genome as an infectious bacterial plasmid that could be manipulated with relative ease by standard molecular biology techniques. This Ad genomic plasmid could be stably...

An Epidemic Of Childhood Obesity

Children's health in the United States has improved dramatically over the past century. Vaccines targeting previously common childhood infections such as measles, polio, diphtheria, tetanus, rubella, and Haemophilus influenza have nearly eliminated these scourges. Through the widespread availability of potable water, improved sanitation, and antibiotics, diarrheal diseases and infectious diseases such as tuberculosis and pneumonia have diminished in frequency and as primary causes of infant and child deaths in the United States (CDC, 1999). Pervasive food scarcity and essential vitamin and mineral deficiencies have largely disappeared in the U.S. population (IOM, 1991 Kessler, 1995). The net result is that infant mortality has been lowered by over 90 percent, contributing to the substantial increase in life expectancy more than 30 years since 1900 (CDC, 1999). Innovations such as seatbelts, child car seats, and bike helmets, meanwhile, have contributed to improved children's safety,...

Prevention of Birth Defects

Because several birth defects are caused by infections, prevention initiatives also emphasize immunization and information. For example, because of widespread vaccination for rubella (German measles), the birth defects caused by this infection rarely occur in the United States. Information about the risk of birth defects resulting from maternal infection with syphilis or other sexually transmitted diseases may stimulate the development of services to help women at greatest risk. Cytomegalovirus, the most common of the congenital viral infections, affects almost 40,000 infants each year. It can be passed through bodily fluids, such as saliva, blood, and breast milk. It is often passed to a pregnant woman from a child who is infected but is not showing symptoms for example, an infected child may sneeze and then touch a pregnant woman, thus infecting her. An infant born to a mother who has contracted cytomegalovirus is at an increased risk for mental retardation and vision or hearing...

Changes in the food production chain and food industry structure

Not all changes in the food production and marketing chain have resulted from technological advances - some changes are due to other factors such as a balancing of global supply and demand for certain food products. Additionally, some changes in the food production chain may increase some food safety risks or alter the mix of risks. For example, the use of aquaculture is becoming more common as wild fisheries become increasingly over-harvested and less cost-effective for some species and areas. US aquaculture production increased by over 50 between 1990 and 2000 (NMFS, 2002) and the aquaculture share of the world production also has increased (FAO, 2000). Farm-raised fish pose a different set of food safety challenges from those of wild-caught fishery products. Farm-raised fish are subject to contamination from residues by production inputs (e.g. vaccines, feed additives, and antibiotics), whereas wild-caught seafood may be more subject to histamine risks from poor temperature control.

Preventive measures that can reduce the cancer burden

Based on the experience gained so far, it is considered that a substantial proportion of the cancer burden worldwide could be prevented if adequately implemented community-based programs for early cancer detection and treatment, tobacco control, cancer-related vaccination (for liver and cervical cancers), and health promotion campaigns (American Cancer Society, 2002 Commission of the European Communities, 2009 WHO, 2009) (Table 3).

Animal Models 431 Rat Mouse

Enteric-coated microspheres have long been administered to rats. Cellulose acetate phthalate (CAP)-coated microspheres administered into the throat of rats resulted in the expected protective benefit of enteric formulation for an acid-labile vaccination of an enterotoxin 64 . More recently, an enteric polymer incorporated into nanospheres was compared to traditional enteric-coated microparticles in the rat. Interestingly, the colon targeting property of the nanospheres was superior to that of the enteric microspheres, resulting in a superior therapeutics efficacy in a rat colitis model 59 .

Summary And Future Directions

This overview of HSV biology and gene transfer has focused on the use of highly defective HSV genomic vectors that are blocked very early in the virus lytic cycle. These vectors express few viral functions and are highly reduced in vector toxicity, even for primary neurons in culture that are readily killed by less-defective HSV vectors. Moreover, these vector backgrounds are suitable for expression of multiple transgenes or single large genes (e.g., dystrophin) in applications where expression of single- or multiple-gene products are required to achieve a therapeutic outcome (e.g., tumor cell killing, vaccination). Expression of these transgenes can be coordinated, even sequentially, using strategies similar to those employed by the virus to regulate its own genes. Expression can also be controlled by drug-sensitive transactivators, which may prove to be important for regulating the timing and duration of transgene expression. HSV vectors may be most suited for expression of genes in...

Target Tissues And Therapeutic Models

Once again, however, clinically it would be desirable to be able to switch the gene off. If a VSV-G lentiviral vector is injected intravenously in a mouse, it localizes mainly to the liver, spleen, and bone marrow (74,127,128). The levels decline somewhat over time in the liver and spleen but may stay at the initial level in the marrow. These levels are not completely consistent but are in the 0.1 to 30 range of total cell sampled. This observation points to some other promising target tissues, namely, liver and bone marrow. The spleen observation raised the possibility of inducing immune responses and has not attracted as much attention, except in vaccine-oriented applications.

Screening of cervical cancer

Conventional Papanicolaou smear testing (Figure 2) (American Cancer Society Guidelines, 2011 ESMO European guidelines for quality assurance, 2010). Also, primary prevention by prophylactic vaccination against the HPV types that are causally linked with most cervical cancers in Europe, HPV-16 and HPV-18, is now commercially available (Schiller & Lowy, 2010). The high efficacy of the vaccines is expected to dramatically decrease cervical cancer, by preventing up to 70 of newly diagnosed cases. However, prophylactic vaccination is performed in young girls and it will take a time until it provides the health gains. Therefore, cervical screening still remains the main preventive option (Figure 2). Nowadays, situation is that the high cost of the vaccine prevents its widespread implementation, which may further increase the gap in cervical cancer statistics between developed and developing countries (Haie-Meder, 2010). Future HPV Vaccine I.HPVTest 2. HPVTest

In Vivo Pathogenicity And Biodistribution

Vaccinia virus has been used as a live vaccine in the smallpox eradication program, and more recently as a vaccine against cancer (49). It has not been widely accepted as a potential tumor-directed gene therapy vector, however, due to concerns regarding the safety of a systemically administered replicating virus. Although it is generally considered to be a relatively safe vector for vaccinations, a defined risk exists for generalized vaccinia, vaccinia-associated encephalitis, vaccinia ne-crosom, and eczema vaccinatum have been described in infants and the immunosuppressed population, specifically those with deficits in cellular immunity (50-55). Vaccinia-associated encephalitis is a recognized complication of smallpox vaccination that can lead to death, and vaccinia can be recovered from the central nervous system (54). Classically, vaccinia infection in immunosuppressed patients leads to a progressive necrotic ulcer known as vaccinia necro-sum. This ulcer can progress to destroy...

Host Immune Response To Vaccinia

The immune response to vaccinia viral vectors serves as our paradoxical friend and foe in attempting to develop them into effective vectors for gene therapy. On the one hand, the vigorous immune response is desirable because we believe that it enhances its potential as a vaccine. On the other hand, the vigorous immune response leads to premature clearance of the virus before adequate levels of replication have occurred, thus decreasing the level of transgene expression and possibly the overall efficacy. the 1970s, young patients will not have been exposed to the virus. Most cancer patients, however, are older and have been exposed to vaccinia. As with other virus vectors, however, reinfection is possible after prior exposure. Laboratory workers and military personnel who undergo revaccination for smallpox usually form pox vesicles in the skin, despite prior vaccination. This has also been demonstrated in tumor vaccine trials in patients previously immunized (60). Workers at vaccine...

Safety Considerations

Safety considerations for cancer gene therapy vectors include direct pathogenicity of the virus, toxicity of the therapeutic gene product, genome insertion with risk for malignant transformation and germ line mutations, teratogenesis, and the ability to recombine with endemic virus or spontaneously mutate to form a more virulent pathogen. Because vaccinia is a cyto-plasmic virus, the viral DNA does not transport to the nucleus and therefore integration into the genome is very unlikely. In addition, there is no known latent infection with vaccinia virus and all cells infected by the virus will be killed by the virus. In addition, because poxviruses are not endemic in the population, it is extremely unlikely for recombinations to occur in patients between attenuated strains and wild-type strains, which would result in a more virulent virus with world health implications (90). The stability of the virus has already been proven during vaccination as part of the smallpox eradication...

Clinical Experience

Smallpox Vaccination Extensive clinical experience exists with vaccinia virus as a vaccine for the eradication of smallpox. The most common commercial preparation used in the United States was the Wyeth Dryvax (101). It is the only vaccine available today. The virus was produced by infection of live calves by dermal scarification, followed by physical scraping of the skin. Future vaccines will be produced on cell lines, and ongoing trials are comparing strains for safety and efficacy (56). The vaccine is delivered by scarification of the skin. The lyophilized virus is reconstituted and spread on the skin. A scarification needle is then used to penetrate the dermis through the vaccinia coat in multiple places. Effective vaccination is indicated by the development of pustules 6 to 10 days after vaccination. The pustules represent replicating vaccinia within the dermis. Live virus can be recovered from the pustules from days 3 through 14 after vaccination. There is a direct...

Divorce and children 151

Alternatively, diphtheria toxoid may be combined with tetanus toxoid alone (DT) and given to children, or combined with tetanus toxoid (Td) in an adult vaccine. The Td version only contains about 15 to 20 percent of the diphtheria toxoid found in the DTaP vaccine and is used for older children and adults. The vaccine, which was introduced more than 50 years ago, led to a dramatic reduction of the incidence of diphtheria throughout the world. Primary preventive programs aimed at immunizing all infants and children in the community have almost eliminated the disease. Yet while the reported incidence of diphtheria has been almost the same since the 1960s, it still occurs in isolated epidemics, primarily because some countries have taken a complacent attitude toward vaccination. The disease continues to represent a serious public health problem because it is possible for even fully immunized people to carry the C. diphtheriae bacteria in nose and throat, transmitting it to non-immunized...

Enhancing Immune Responses Toward Tumors By Bacterial Infections

As a logical consequence, bacteria are now widely used as delivery system for various vaccination strategies, including immunizations against model tumors (34). This was recently extended to genetic vaccination (i.e., bacteria have been used as vehicles for transfer of eukaryotic expression plasmids encoding tumor antigens or immune stimulatory molecules). Obviously, the combination of the adjuvancy of a bacterial carrier and particular features of the antigen expression plasmid should synergize to induce protective antitumor responses. During bacteria-mediated DNA vaccination, DCs might acquire the tumor antigens from the bacterial carrier either by direct infection or via cross-presentation. In the latter case, the infected cell that contains the antigen is phagocytosed by neighboring DCs, which then are activated and represent the original antigens. Both routes, cross-priming and direct priming have been described for specific activation of T cells. In addition to genetic...

The Medical Equivalent of Shock and

There are other factors that often slow work for scientists. Laboratories are exceptionally expensive places to run, and scientists are often in competition with one another to find a new medicine or vaccine that can bring in funds for research. For that reason, research facilities are rarely willing to consolidate or share information, since they view one another as rivals. And because there is no greater achievement for a scientist than discovering a pathogen or its cure, the scientists themselves are often competitors.

Potential Clinical Applications

The highly efficient delivery in vitro has resulted in the development of other ex vivo approaches. For example, treatment for malignant melanoma has been designed by application of gene-modified cancer cell vaccines. DNA complexes are used to deliver immunostimulators genes (e.g., interleukin-2) into melanoma cells in vitro. After irradiation (to block tumor cell growth), the transfected cells are applied in vivo to trigger an antitumor immune response. This treatment has been translated into a medical protocol and is being evaluated in clinical trials (169,170).

Specific immunotherapy

Specific immunotherapy, which seems be more important in cancer treatment research, could be divide into 3 parts monoclonal antibody, adoptive cellular therapy, and vaccine. Infusion of antibody or activated cells is called Passive Immunotherapy, on the other, vaccine can induce active immunotherapy. The simplest model of immune cell-mediated antigen-specific tumor rejection consists of three elements appropriate antigen specific for the tumor, efficient antigen presentation and the generation of potent effector cells.

Adverse Effects And Reactions Allergies And Toxicity

Management of Abrus lectin poisoning is symptomatic and supportive. Investigations showed that vaccination with abrin toxoid or administration of ascorbate may offer some protection against a subsequent abrin challenge (Dickers et al., 2003). The sub-lethal doses of lectins showed potent antitumor and immunostumulatory responses, and the therapeutic effect of Abrus lectins can be obtained by masking the undesired toxic effect of lectins. Clinical trials showed that the human minimum lethal dose of ABR by intravenous injection is 0.3 mg kg as an immunotoxin for cancer treatment. The report showed that patients tolerated a dose of 0.3 mg kg without serious adverse effects (Gill, 1982).

Epidemiology of Variant CJD and Other Human TSEs Variant CJD

Early in the vCJD epidemic, three factors predisposing to the disease became evident residence in the United Kingdom, methionine homozygosity at codon 129 of the prion protein gene and the relative young age of the individuals compared with sporadic CJD. In addition to these, a range of hypotheses were generated concerning risk factors relating to possible routes of exposure to the BSE agent, to predisposing factors or to other unrelated possible causes of the disease, such as exposure to organophosphates. Possible routes of exposure to the BSE agent included the most likely, which was through diet, and others such as surgery, medicines, including vaccines, certain occupations having contact with cattle, meat or products manufactured from cattle meat (for example farmers, abattoir workers, butchers and laboratory workers) and contact with animals. Factors that were considered as predisposing factors included social class, ethnicity and urban rural residence.

Other Cancer Treatments

Vaccines are also used to stimulate the immune system. Interferons, chemical messengers used to fight viruses, inhibit tumor cells from reproducing. Hormonal treatments are also under study. Hormones are substances secreted by certain glands that pass into the blood and stimulate the action of specific organs. It has been shown that certain hormones made by the testes and ovaries can influence the growth of tumors in the breast and prostate. Today, instead of surgically removing the testes or ovaries, drugs are used to block the effects of these hormones.

Applications Of Gene Guns In The Immune System

Essentially in parallel in the 1980s. With the advent of these approaches, it became theoretically possible to use them to deliver antigen genes into the cells of a host to provoke immune responses. Genetic immunization is performed by introducing the gene(s) for protein antigens into the host animal rather than introducing the antigen itself. Once the plasmid is delivered into the host cell, the gene is expressed and produces the antigen intracellularly. The process therefore essentially uses the host animal itself as a bioreactor to generate its own vaccine antigens to drive both antibody and cellular immune responses. The first published demonstration of this novel approach to immunization was by Stephen Johnston's group (26). In this first paper published in 1992, the ''wand'' gene gun (Fig. 3B) was used to deliver plasmids encoding human growth hormone and human a1-antitrypsin into the skin of mice. This in situ gene delivery allowed the host cells to produce these secreted...

BSE Epidemic and Relationship to Variant CJD

Although the most probable route of transmission of BSE to humans was through diet, other possibilities were considered, such as through medicines, including vaccines, that contained products prepared from cattle and through contact with cattle (butchers, farmers, abattoir workers). In addition, transmission through an intermediate species, such as cats, and transmission to cattle and humans from a third species, such as from scrapie in sheep, were also considered as possible methods of transmission. A UK case-control study was established in 1998 to examine these and other risk factors for vCJD (see above, Ward et al., 2006).

Immunizations for health care professionals

Include the HEPATITIS B vaccine (Recombivax or EngerixB) in a three-dose series INFLUENZA vaccine every fall MMR (measles-mumps-rubella) vaccine unless there is proof of immunity and Td. See also IMMUNIZATION VACCINE. immunizations for homosexual males heterosexuals with multiple partners Anyone with this sexual history should receive the HEPATITIS B vaccine in a three-dose series, plus routine vaccines recommended for adults. See also IMMUNIZATION VACCINE.

PSA in the era of biologic and targeted therapy

Two vaccine trials, Sipuleucel-T (Provenge) 43, 44, 45 and the TRICOM PROSTVAC 46, 47 demonstrated a significant overall survival benefit without any consistent decline in PSA, raising questions about the value of PSA response for non-hormonal, non-cytotoxic therapies. In addition, wide fluctuations have been observed in PSA values due to a transient effect of some drugs on PSA production seemingly independent of cell proliferation. The independent, non-proliferative effect of drugs on PSA expression should be considered when interpreting PSA response data. These aberrant PSA effects must be considered together with imaging results and clinical evaluation of the patient. Nevertheless, it has been consistent that post therapy a > 50 PSA decline in pre-treatment PSA carries a significant overall survival advantage 48, 35 .

Cancer immunotherapy protocols

Strong antitumor effects, however, were not observed in the reported clinical trials. In pancreatic cancer, vaccination with GM-CSF transduced allogeneic pancreatic cancer cell lines along with adjuvant radiation and chemotherapy following surgical excision demonstrated possible benefit in disease-free survival, which appeared to be associated with the increase of postvaccination DTH responses against autologous tumor cells.

Immunomodula Tion

Red ginseng powder has been shown to restore immunity after chemotherapy and reduce the recurrence of stage III gastric cancer. The 5-year disease-free survival and overall survival rates were significantly higher in patients taking the red ginseng powder during postoperative chemotherapy versus control (68.2 vs 33.3 , 76.4 vs 38.5 , respectively, P < 0.05). Despite the limitation of a small number of patients (n 42), these findings suggest that red ginseng powder may help to improve postoperative survival in these patients. Additionally, red ginseng powder may have some immunomodulatory properties associated with CD3 and CD4 activity in patients with advanced gastric cancer during postoperative chemotherapy (Suh et al 2002). Vaccine adjuvant activity Ginseng extract (100 mg ginsan G11 5 day) improved the response to an influenza vaccine in a multicentre, randomised, double-blind, placebo-controlled two-arm study of 227 subjects. Compared with vaccine without the ginseng, the...

Targeting signalling molecules

Preclinical evidence has also shown that specific inhibitors of these signalling pathways can also increase immune activation. For example, VEGF is a key inhibitor of pro-inflammatory cytokines as well as dendritic-cell maturation, and it can also directly inhibit T-cell development. So antibodies that block signalling by this growth factor can promote antitumour immune responses. Furthermore, downregulation of the ERBB-receptor-family members with drugs such as herceptin promotes tumour-antigen presentation by HLA class I molecules, improving the potential for T-cell recognition and lysis118onoclonal antibodies that target these signalling pathways are now being developed for clinical trials as agents that potentially synergize with other immune-based approaches, including vaccines.

New Weapons Against HIV

On April 23, 1984, Secretary of Health and Human Services Margaret Heckler announced that the virus that caused AIDS had been discovered and that scientists had perfected a process that enabled them to grow large quantities of the virus in order to study and characterize it. She also declared, We . . . believe that the new process will enable us to develop a vaccine to prevent AIDS in the future. We hope to have such a vaccine ready for testing in approximately two years.21 Her final prediction was that there will be a . . . cure for AIDS before 1990.22 Unfortunately, for the thousands of AIDS victims, families, and others who dealt with the human tragedy of the disease every day, Heckler's predictions were far too optimistic. Two decades later, Heckler's words still echo as a constant reminder of how much more complicated HIV has proven to be than scientists first estimated. As of 2004, HIV vaccines were still in development, over 22 million people worldwide had died of AIDS, and...

New immunotherapy targets

A relatively newer, more promising method of tumour-antigen identification is the use of the patient's lymphocytes to evaluate proteins that are found to be differentially expressed by pancreatic cancer157-158 approach has several advantages. First, it allows for a rapid screen of a large number of candidate antigens but requires the isolation from patients of only a few lymphocytes, which are limited in availability. Second, this approach is not dependent on the availability of autologous tumour cells, which are difficult to isolate in large enough numbers for generating cDNA libraries. Third, this approach can be used to identify tumour antigens that are expressed by any HLA type, allowing for the generalization of this approach to most patients. Finally, this approach has the potential to rapidly identify 'immune relevant' antigens, as it uses immunized lymphocytes from patients vaccinated with a whole-tumour-cell vaccine approach who ideally have demonstrated clinical evidence of...

Habits vs Mental Problems

Child in every 20 who gets meningitis dies, and up to 35 percent of those who live develop permanent brain damage. However, widespread use of a vaccine licensed for infants in 1990 has dramatically reduced the incidence of a deadly disease that only 10 years ago killed 800 infants each year in the United States. According to the CDC, the incidence of invasive Hib infection has dropped by almost 98 percent among infants and children since the introduction of the vaccine. Although the disease is not yet completely eradicated, the vaccine has been stunningly effective.

What is the role of the immune system in MS

The occurrence of inflammatory disease of the brain and spinal cord (acute encephalomyelitis) following infections and immunizations (especially after a killed virus rabies vaccine made from rabbit spinal cord) led to studies of the allergic potential of certain proteins in the nervous system. Most research has been focused on a single protein, myelin basic protein, because it has a high potential for the induction of experimental demyelinating disease in rats, guinea pigs, monkeys, and other animals. Only 10 millionths of a gram (there are 450 grams in a pound) injected into a genetically susceptible rat can result in experimental disease resembling MS. Over 30 years ago we found that MS patients have cells reactive to this protein in their blood. More recently, Swedish scientists have also found cells with similar reactivity in the spinal fluid of MS patients. Importantly, the original research into a treatment now approved for use in MS (Copaxone) arose from this work. Copaxone is...

General Strategies For Suicide Gene Therapy

Two basic strategies exist for cancer gene therapy. The first conceived strategy is ''ex vivo'' gene therapy in which a tumor or fibrous tissue biopsy is taken from a cancer patient whereupon individual tumor cells or fibroblasts are isolated and grown in vitro (Fig. 3). Therapeutic genes are then inserted into these cells typically using retroviral vector infection in tissue culture. The cells are subsequently irradiated and then reimplanted into the original tumor site or distant to the tumor site by autologous transplantation. The level of irradiation is controlled so as not to immediately kill the cells but to prevent growth and allow only a short period of survival after reimplantation. This strategy has been more commonly applied to classic cancer vaccine and cytokine gene therapy strategies. Although this approach is feasible with suicide gene therapy, the predominant tumor response would come from a metabolic cooperation or immune bystander effect subsequent to prodrug

Pylori vs Campylobacter Pylori

There is no vaccine against H. pylori. Although research suggests that infection is passed from person to person, scientists do not really know exactly how this happens, so it is difficult to present prevention guidelines. However, it is always important to wash hands thoroughly, eat food that has been properly prepared, and drink water from a safe source.

New therapeutics settings in the treatment of castration resistant prostate cancer

The growth of prostate cancer is originally androgen dependent and metastatic tumors are generally treated with androgen ablation therapy, with or without antiandrogen supplementation 41, 42, 43 . However, resistance to hormonal therapy occurs within 12-18 months (remissions last on average 2-3 years, progression occurs even under castration 37, 44, 45 , referred to as hormone-refractory or CRPC 41 . Resistance to hormones (in patients with metastatic disease) is probably shorter than 2-3 years, using PSA. Until recently, patients with castration-resistant prostate cancer had limited treatment options after docetaxel chemotherapy. However, in 2010, new options emerged 46 . The three nonhormonal systemic approaches that have been found to prolong survival are docetaxel as first line 4 chemotherapy, cabazitaxel as second-line cytotoxic chemotherapy 46, 47 and a vaccine named si-puleucel-T 48 . A new hormonal manipulation with abiraterone acetate 45 also showed to prolong survival in...

Fat across the Species Barrier

But, of course, no greater magic bullet can be imagined for human obesity than an antiviral agent that would simply cure obesity or even a vaccine that could prevent it. In 10 years, Dhurandhar stated, people may be able to walk into a clinic and be told that their obesity is due to X cause, such as genes, the endocrine system, or pathogens. That may have a more productive outcome than a blanket treatment right now, which is not very successful. And because viruses are hard or impossible to treat, prevention through vaccines will be key. Does the anxiety about barriers to disease not lie at the heart of our desire that obesity, too, can be quickly fixed, once it is recognized as merely an infectious disease, rather than a reflex of national or personal character The quick fix here is not to repair the food chain or end fast food, but to change the world so that such depression is eliminated. No quick fix is promised why not hope for a vaccine against modernity, hopelessness, and fat...

Psychosocial Interventions For Survivors With Advanced Cancer

Emotionally expressive writing is an intervention that has been considered as a potentially cost-effective and minimally invasive psychosocial treatment for AC patients. In this paradigm, participants are assigned to write about either their deepest thoughts and feelings about their cancer or to write about a neutral control topic (e.g., a different health behavior) for 20 minutes across four writing sessions. Like SET, expressive writing also allows individuals living with AC to confront cancer-related thoughts and feelings, put their experience into words, and integrate cancer into their life story. To date, one pilot trial of expressive writing has been conducted in AC patients. This trial, conducted in a sample of metastatic renal cell carcinoma patients enrolled in a clinical vaccine trial, demonstrated no intervention effect on perceived stress or mood disturbance but did suggest that patients who wrote about their cancer experienced better sleep quality and greater vigor...

Respiratory Mucosal Immunity Neuronal Innervation and Its Stress Related Perturbations

Since stress is such a potent modulator of the immune response and its effector mechanisms (Elenkov et al. 2000), it follows that it may be a contributor to the success of immunization, a mainstay strategy in the prevention of respiratory infections such as influenza and pneumococcal disease. In a recent trial involving young adults receiving the hepatitis B vaccine, those subjects experiencing psychological distress had significantly lower specific antibody responsiveness (Marsland et al. 2006). Drummond and Hewson-Bower (1997) found a correlation between lower serum IgA albumin ratio and stress in children with recurrent upper respiratory tract infections. Another study concluded that a healthy individual's increased sociability decreased the risk of viral upper respiratory tract infection (Cohen et al. 2003).

Dendritic Cell Interactions and Cytokine Production

The immune system has developed mechanisms to detect and initiate responses to a continual barrage of immunological challenges. Dendritic cells play a major role as immunosurveillance agents. To accomplish this function, DCs are equipped with highly efficient mechanisms to detect pathogens, to capture, process, and present antigens, and to initiate T cell responses. The recognition of molecular signatures of potential pathogens, in DCs, is accomplished by membrane receptor of the toll-like family (TLRs), which activates dendritic cells, leading to the initiation of adaptive immunity. TLR signaling in DCs causes an increase in display of MHC peptide ligands for T cell recognition, upregulation of costimulatory molecules important for T cell clonal expansion and secretion of immunomodulatory cytokines, which direct T cell differentiation into effectors. Remarkably, ligation of distinct TLRs can trigger differential cytokine production in a single DC type or result in different cytokines...

March of Dimes Birth Defects Foundation A

The March of Dimes was founded in January 1938, when President Franklin D. Roosevelt, himself a polio victim and alarmed by decades of worsening polio epidemics, established the National Foundation for infantile Paralysis. At the time, comedian Eddie Cantor coined the phrase March of Dimes (playing on the popular newsreel feature The March of Time), appealing to radio listeners all over the country to send their dimes directly to the White House. The campaign was extremely successful, and over the next 17 years, the National Foundation focused on funding research to develop a vaccine against polio. In 1948, with funding provided by the March of Dimes, Dr. Jonas Salk was able to grow the three known types of polio virus in his lab and eventually to develop an experimental killed-virus vaccine. In the summer of 1952 Dr. Salk tested the vaccine on children who had already recovered from polio. Following vaccination, the level of polio antibodies in their blood increased. The next step...

Sexually Transmitted Diseases

There are many types of STDs which can affect youth and over half of STDs occur to adolescents (1,3,29-31). The majority of STDs involve individuals aged 15 to 29 years. Each year, 1 in 20 adolescents in the world obtains a curable STD (3). STDs can be asymptomatic and youth often do not seek treatment even if symptomatic. Adolescents are less likely than adults to use protection (i.e., condoms). The most common STDs among youth are infections due to human papillomavirus (HPV), herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. HPV is main cause of cervical cancer in females under 30 years of age and the recently developed HPV vaccine can prevent 70 of these cervical cancers. It is important to provide STD services to adolescents around the world in a confidential manner that provides enough time to manage the youth properly. Primary prevention involves confidential youth counseling about STDs proper immunizations (including hepatitis A and...

Natural Compounds Antioxidant and Antiandrogens in the Prevention of Prostate Cancer In vivo Evidences from Murine

Preventive agents in humans are hampered by the long latency period and challenging epidemiological problems, reliable preclinical models can be useful to overcome these problems. Early prostate tumorigenesis is apparently characterised by dysplasia that starts with proliferative inflammatory atrophy as the prelude to low-grade Prostatic Intraepithelial Neoplasia (PIN), high-grade PIN, primary cancer, metastatic cancer, and hormone-refractory cancer. During this progression, genetic damage accumulates within cancer cells 3,4 . Animal modelling has made a significant contribution to the study of prostate development and disease. Identification of the molecular features of PCa pathogenesis and progression could be greatly facilitated by laboratory and clinical models. However, a prerequisite for the elaboration of useful models is a better understanding of the molecular characteristics of human PCa. This puzzle, in addition to the well-known inter- and intra-individual heterogeneity of...

Diagnosis And Treatment The Infectious Etiologies

Tympanostomy tube drainage is not uncommon, and typically occurs in two patterns. It has been estimated that 10 of all tubes drain during the first week after surgery. The fact that antibiotic eardrops and nonantibiotic eardrops are equally effective at controlling this drainage suggests that most of this early drainage is sterile fluid or treated acute otitis media fluid that has been sterilized (10). As for latter drainage, that fluid has been cultured and the most common pathogens found have been Streptococcus pneumonia and Haemophilus influenza (11). Antibiotic-containing eardrops approved for middle-ear use are the most effective treatment option for this drainage. In cases that are refractory to antibiotic eardrops, we add oral antibiotics and, if these fail, we consider changing the tubes. As new vaccination patterns emerge, the predominant microorganisms found in middle-ear secretions may change over time. Finally, in chronic otitis media with cholesteatoma, the middle ear is,...

Materials And Methods

Immunogens and Immunization Procedures. Escherichia coli ribosomal proteins L7 and L12 were extracted (10) from 50S subunits and purified as described (11) by ion-exchange chromatography on carboxymethyl- and DEAE-cellulose. Antibodies were raised in a goat by injecting 250 fig of protein emulsified with complete Freund's adjuvant intracutaneously distributed over several sites. Bacillus pertussis vaccine (1.5 ml of Bordet-Gengou vaccine, Schweizerisches Serum- und Impfinstitut, Bern, Switzerland) was given subcutaneously with every antigen injection. Booster injections of the same formulation were given on days 38,79, and 110. The animal was bled on day 117.

Microbial iron acquisition

Iron is essential to all microorganisms. The low concentration of free iron in body fluids creates bacteriostatic conditions for many microorganisms and is therefore an important defense factor of the body against invading bacteria. Iron-binding proteins, such as LF, TF, and ferritin, play a central role in human ferrokinetics. These iron-binding proteins also participate in the process of decreasing iron availability for the microorganisms. LF and TF restrict the amount of ionic iron available in body fluids to 1018 M (Bullen, 1981). They do so by decreasing iron re-utilization. Anemia of inflammation (previously called anemia of chronic disease) is seen in the setting of infectious, inflammatory, and neoplastic diseases. It results, in part, from changes in the intracellular metabolism of iron. Alterations of iron physiology seen in many clinical circumstances make excess iron available to microorganisms, thus enhancing their pathogenicity. Understanding the molecular basis of iron...

Induction Of Immune Responses In Primates

It would be desirable to evaluate in primates DNA vaccine constructs that induced high levels of immune responses in mice. Nonhuman primates represent the most relevant animal challenge model for HIV vaccine studies. Specifically, there are currently 3 different primate models for HIV vaccine studies. They include the HIV challenge model in chimpanzees and the SIV and chimeric SIV HIV-1 (SHIV-1) challenge models in macaques. Chimpanzees can be infected by HIV isolates from humans, although they do not readily develop AIDS-like disease. However, the SIV challenge model uses the macaque SIV, which replicates to high levels and causes an AIDS-like disease in both cynomolgus and rhesus macaques. The chimeric SHIV viruses were constructed by replacing SIV envelope genes with specific HIV-1 envelope genes (117). The SHIV viruses replicate in macaques similarly to SIV and represent an infectious challenge model for HIV-1 envelope-based vaccines. Importantly, certain SHIV strains such as SHIV...

Use Of Molecular Adjuvants In Primates

Kine genes could also be achieved in rhesus macaques. DNA vaccines for HIV env rev and SIV gag pol alone were evaluated for their immunogenicity and compared with these vaccines, which also included IL-2, IFN-7 (Th1), or IL-4 (Th2) cytokine cDNA constructs (171). The cytokines dramatically enhanced seroconversion induced by the vaccines and appeared to modulate cellular responses as well, although more modestly. Vaccinated animals were challenged intravenously with SHIVIIIB. Half of the animals in the vaccine or vaccine plus Th1 cytokine groups exhibited protection from infection based on sensitive limiting dilution coculture, demonstrating a dramatic effect on viral replication of the vaccines tested. The protected animals were reboosted with SIV DNA vaccines (SIV and cytokine constructs) and were rechallenged intravenously with pathogenic SIVmac239. All vaccinated animals were negative for viral coculture and antigenemia. In contrast, the control animals exhibited antigenemia by 2...

Fecaloral transmission route

Primary barriers to keep the infectious organisms out of the environment or when the primary barrier works imperfectly. Secondary barriers are those interventions that prevent viruses from infecting another host once the viruses are in the environment. Examples of these secondary barriers may include avoiding unsafe foods (e.g. raw shellfish) or destruction of viruses (e.g. cooking foods, hand-washing). Vaccination may also be a secondary barrier. Effective interventions that inactivate viruses are listed in Table 14.2. In addition, two reviews on the effects of water and sanitation on enteric illness morbidity list several interventions (e.g. good water quality, hand-washing, safe excreta disposal) that could interrupt the fecal-oral transmission route.60'61

Water contaminated 297

Anyone who has genital warts or who has been diagnosed in the past should always use a condom during sexual intercourse. At present, there is no way to prevent the disease. Physicians at the University of Rochester Medical Center are beginning the world's first test in humans of a potential vaccine to protect against the virus.

Epidemiologic factors

It is hypothesized that different strains have different predominant transmission routes, infectivity, and clinical manifestations. We speculate that virus strains differ in other virulence aspects including longer shedding times, shedding higher titers, and longer persistence in the environment. In addition, host determinants of resistance and susceptibility (genetic and immunologic) are probably different for each strain (reviewed in Hutson et al90). The genetic differences among NoV strains create challenges for the development of a pan NoV vaccine (reviewed in Hutson et al. ,90 Matsui and Greenberg,91 Tacket et al.,92 Estes et al.,93 and Tacket94). It is possible that NoV vaccine development may follow the influenza vaccine model, in which yearly flu vaccines are developed for the predominant strains. Only one serotype of hepatitis A virus has been found of which the antigenicity is determined by an immunodominant epitope. Four distinct genotypes of...

Implications and future studies 1461 Implications for prevention

Providing ongoing education about the causes of food contamination and pathogen transmission, and maintaining open channels of communication with public health officials to report and identify foodborne outbreaks. The food service industry may want to consult the 2005 edition (updated every four years) of the Food Code. This Code is published by the FDA, USDA, and CDC and is a reference manual for regulatory agencies that ensure food safety in food service establishments, retail food stores, other food establishments at the retail level, and institutions, such as nursing homes and child-care centers. This Code has evidence-based, practical recommendations for addressing risk factors associated with foodborne illness. In addition, mandatory vaccination (i.e. hepatitis A vaccination) of all food handlers would also reduce the risk of foodborne transmission of this virus. For example, St. Louis, Missouri, and the state of Nevada require all food handlers to receive hepatitis A...

Early Disappointments

In 1992, human clinical trials of AIDSVAX, a vaccine developed by a California company called VaxGen, began. Specific for strains of HIV common in North America, AIDSVAX was made of synthetic proteins that are copies of a protein found on the surface of HIV. This surface protein, called gp120, facilitates the binding of HIV to helper T cells. AIDSVAX essentially tricked the immune system into mounting an immune response against the synthetic gp120 proteins, even though there was no accompanying HIV infection. Since only gp120 viral proteins are introduced, patients could not get AIDS from the vaccine. Rather, the hope was that the vaccine recipient would get a head start in developing HIV-specific antibodies, and presumably, real HIV particles would be destroyed in the bloodstream before infection could occur. After it was proven safe in the first two phases of clinical trials, AIDSVAX became the first AIDS vaccine to enter the final phase of testing. Two large-scale trials were put...

Exploiting a Natural Immunity

While AIDSVAX was being tested, another very different vaccine was being developed. Doctors in Nairobi, Kenya, had noticed that about 5 percent of the two thousand prostitutes studied at an HIV clinic seemed to have developed a natural immunity against the virus. Though these women were repeatedly exposed to HIV, they remained uninfected. As the director of the clinic, Dr. Omu Anzale, Researchers at the United Kingdom's Oxford University and at the University of Nairobi, in partnership with the IAVI, developed a vaccine meant to mimic the resistance seen in the Nairobi women. The researchers designed the vaccine, named DNA-MVA, based on the A strain of HIV, the dominant strain found in Kenya and much of eastern Africa. DNA-MVA would introduce portions of HIV viral DNA into the recipient. Rather than using viral proteins directly as happened with AIDSVAX, with DNA-MVA, viral proteins are produced when the viral DNA enters the recipient's cells. The presence of these foreign proteins...

The Chemotherapy Of Cancer

9.6.4 Immunotherapy and vaccines 339 9.17.10 Vaccines 9.6.4 Immunotherapy and vaccines The aim of immunotherapy is to stimulate the body's natural response to fighting the cancer. Several neoplasms, including some types of breast cancer, have been found to possess specific tumour antigens, and this has led to the development of monoclonal antibodies specific for some tumour types. Although little success has so far been achieved by treating patients with antibodies alone, research is still ongoing into the development of vaccines that may either prevent tumour formation or modify the growth of established tumours. In the latter case, there has been recent publicity over the use of a vaccine to prolong the life of melanoma patients. Tumour-specific antibodies have also been used for drug targeting by attaching them to either drugs or enzymes (e.g. ADEPT), and these strategies are discussed later.

Factors contributing to the pathogenicity of viral foodborne diseases

Most foodborne viruses belong to the picornavirus' calicivirus' and reovirus families (Table 15.1). The total number of illnesses caused by these viruses has been estimated to be upwards of 30 million cases per year in the United States. However' most estimates indicate foods as a primary source of infection in only 5-6 of the incidences.75'186'221 For reasons to be discussed in Section 15.6' direct demonstration of the presence of viruses in foods implicated in foodborne outbreaks have been achieved only in a few instances.125'182'195 In terms of sheer numbers' Norwalk virus (NV) within the genus norovirus (NoV) is responsible for the vast majority of foodborne illnesses in the United States' followed by astro- and rotaviruses.221 Hepatitis A virus comes in at a distant fourth' and the numbers have dropped somewhat following the development of an effective vaccine.12 However' like many enteric viruses' the number of asymptomatic infections is high' and the reported cases may not...

Viral genes and pathogenicity

And host shut-off, , although such differences may be cell-line specific. Clearly, IRES efficiency in vitro is not the sole determinant of pathogenicity in susceptible animals. The importance of other mechanisms is emphasized by the isolation of a recombinant vaccine derived poliovirus (VDPV) from a child with paralytic poliomyelitis that had the Sabin type-3 capsid antigenic site replaced by a Type II site due to recombination.215 Remarkably, a six amino acid change in the antigenic site 1 of PV-1 (Mahoney) by the sequence of PV-2 (Lansing) rendered the non-pathogenic Mahoney strain to neurovirulence in mice.214

Diseases and pollution

With such a huge demand for disease control, more veterinary medicine companies are using biotechnology to find new ways of growing healthy fish, based on natural differences between resistant and susceptible animals. Vaccination is a key area of disease prevention, aimed at producing immune fish with less need for antibiotics and other drugs. Antiviral vaccines, for example, have been mass-produced by cloning parts of the viral protein coat in bacterial cultures.

Building better trees

Pests and diseases have always been a major threat to tree nurseries and reforestation sites, and biotechnology has added tools such as genetic modification and vaccination to the traditional weapons of chemical sprays. Spruce trees genetically engineered to resist spruce bud-worm infestation were first developed in 1993. Another

Food and Drug Administration Regulatory Authority

Since the beginning of recorded history, societies have been concerned about the purity of the food and drink available to the public. Regulation of food in the United States dates back to early colonial times. Federal controls over the drug supply started in 1848 when the state of California passed a pure food and drink law. In 1902, Congress made appropriations to establish food standards in the same year, the Biologics Control Act was passed to license and regulate interstate sale of serum, vaccines, and other biologics used to prevent or treat disease in humans. The 1902 act established federal inspection of licensed facilities, prohibition of false labeling, and the concept of a dating period during which a biological product would be medically used. In 1906, the Food and Drug Act passed Congress, prohibiting interstate commerce of mis-branded and adulterated foods, drinks, and drugs. In 1938, the Federal Food, Drug, and Cosmetic (FD& C) Act was enacted, making the 1906 Food...

Mechanisms of virusinduced damage to host cell 1551 Apoptosis as a pathogenic mechanism

Enterocytic-like cell lines and in the mouse central nervous system. ' Apoptosis resulting from activation of the caspase pathway by the perforin granzyme route was reported following vaccination with oral polio vaccine. IFN7 secretion by both CD4+ and CD8+ T cells was involved' again pointing to apoptosis as a mechanism of tissue damage probably as a result of replication of the vaccine derived virus.324 In contrast' wild-type and most cell culture-adapted HAV strains produce a noncytolytic persistent infection in vitro. A few cytopathic strains of HAV are capable of cell killing in vitro as a result of a slowly developing apoptosis.47'124'126'187 However unlike the enteroviruses' the relationship between apoptosis and pathogenicity in animal models has not been clearly established for HAV.

Respiratory tract infections

Synagis and RespiGam are not vaccinations, but they can help protect high-risk children under age two from the most serious complications. Injections of either of these drugs are typically given once a month during the RSV season (November through May). One injection protects the baby for one month, so an injection is needed every month during the RSV season to be fully protected. No vaccine for RSV currently exists, although some researchers are testing various versions of a live attenuated RSV vaccine. Because RSV spreads in fluids from the nose and throat of an infected person, washing hands and avoiding touching nose or eyes after contact with someone with RSV can help prevent the spread of the disease. Since a baby is most vulnerable during the first three months of life (especially those born during the winter), it is possible to take some steps to protect the baby by

Cocaine Pharmacotherapy

A wide range of pharmacological agents besides antidepressants have been tried as treatments for cocaine abuse and addiction. In general, agents include drugs that affect the production, release, reabsorption, and breakdown of dopamine, serotonin, and other neurotransmitters (Harvard Mental Health Letter, December 1999). Researchers are also evaluating medications that work as a vaccine to prevent the effects of cocaine (Vaccine Weekly, May 4, 1998).

Combining Prevention and Therapy

It's pretty hard to justify or explain how we are on the verge of the worst epidemic in human history, that is preventable, where we have medicine that helps, replete with examples where the epidemic has been turned back. Some of the questions have to be answered by science, with continued progress in treatment therapies and the development of vaccines and cures. But the other questions have to be answered by politics and citizen action.51

Current research frontiers

Will not be easily amenable to control by currently available vaccines. Major efforts will be needed to develop virus isolation and detection protocols capable of detecting such mutated or recombinant viruses in a short period of time.63 As discussed in Section 15.6, vaccine research, specifically DNA vaccines and vaccine cytokine combinations to augment the effectiveness of vaccinations, will remain an important area of investigation. Modulation of cytokine levels (IFN and interleukins) to control viral infections and also nonviral diseases is still in its infancy, and will undoubtedly be an active area of research.2'108'162'248'315

New Tools to Fight SARS

If or when SARS does make a comeback, scientists are banking on new tools with which to fight it. Although experts predict a vaccine will not be available until at least 2006, there are other things that could be valuable in saving lives. One would be an accurate test for SARS. Tests at the current time are not accurate unless a patient has been infected for at least twelve days. In that time, that patient will have infected dozens of other people. Doctors are working to develop a vaccine against SARS and are researching the use of antibodies to help infected patients fight the disease. Doctors are working to develop a vaccine against SARS and are researching the use of antibodies to help infected patients fight the disease. One very promising study by the University of Massachusetts Medical School is looking at producing antibodies, which are normally made by the body as it fights an infection. If antibodies could be produced in a laboratory, there might be a way to give an injection...

Implications for foodborne disease treatment and prevention

Vaccination strategies are an alternative strategy to prevent parasitic infection. Vaccines for nematodes, cestodes, trematodes, and protozoans are slow in development for a variety of reasons, including the lack of appropriate animal models, lack of immune response against certain organisms, and the lack of sufficient interest from commercial industry because of their low profit potential. Also, most humans are able to be infected multiple times by some parasites therefore, there is no lasting protective immunity in hosts, the basic foundation for vaccines (WHO, 1995). Despite these problems, some researchers have been successful in the initial development of some vaccines. For instance, there have been efforts to identify 'hidden' antigens not present on the outer surface of nematodes that produce a protective immune response (Munn, 1997). Furthermore, recombinant oncosphere antigens have been used successfully as vaccines against T. solium and E. granulosus in animal intermediate...

The Future of AIDS

Toxoplasmosis A rare parasitic disease that usually causes no negative symptoms in healthy people but can cause serious health complications in AIDS patients. transfusion The process by which blood from a donor is transferred intravenously to a recipient. vaccine A substance that, when administered into the body, elicits an immune response, usually against a particular disease-causing microorganism.

Experimental Animal Data

Early studies established that moderate, chronic deficiencies of protein and other nutrients (e.g., zinc) could be induced in guinea pigs, and that the resulting nutritional states had many of the metabolic hallmarks of human dietary deficiencies. In general, the design of these experiments called for giving BCG vaccine to one group of guinea pigs among a larger group receiving different diet treatments and measuring a number of antigen-specific immune responses in vitro and in vivo several weeks later. Groups of vaccinated and nonvaccinated animals from each diet group were then challenged with an aerosol containing a low dose of virulent M. tuberculosis. The ability of the guinea pigs to control the infection was assessed quantitatively by culture of viable mycobacteria from the lungs and spleens. It should be noted that the profound loss of T cell-mediated resistance that accompanies chronic dietary protein deprivation in this model is substantially and rapidly reversible....

Q What other animaluse regulations does the FDA impose

Vaccine study of human malignant melanoma Visceral metastases from malignant melanoma is invariably a fatal circumstance for which there is no effective treatment. Using harvested lymph nodes you would like to develop a vaccine. The purpose of the study is to test whether or not the vaccine can prevent the development of visceral metastases.

Q What is your study design

A Portions of melanoma obtained either from biopsies or from operative specimens will be processed and prepared as single cells to be frozen in liquid nitrogen. Patients will be randomized to receive vaccine or a placebo. Patients will be followed for development of metastases. In addition, periodic blood samples will be taken to look for evidence of immunity. Genetic analysis of the tumors will be carried out to see if markers can identify patients who are likely to respond to the vaccination procedure.

The Regulatory Process

In the PR HACCP rule, FSIS stated that they were working with industry, academia, and governmental agencies to develop andfoster measures that can be taken on the farm and through distribution and marketing of animals to reduce food safety hazards associated with animals presented for slaughter. Twelve years have yet to deliver the interventions that can be used on the farm and throughout distribution and marketing of animals, although finally in February 2008 USDA granted a conditional license to Bioniche, a Canadian biopharma-ceutical company, for its Escherichia coli O157 H7 cattle vaccine to collect data to move the product to full licensure. FSIS (1998a) stated that the PR HACCP regulations provide enormous flexibility for the industry to develop and implement innovative measures for producing safe foods.'' Despite the creation in 2003 of the Office of New Technology within FSIS, there have been examples of relatively straightforward interventions (e.g., higher levels of organic...

Q What are the safety concerns

In a study involving biologic materials such as this vaccine trial for example, you will need to provide evidence of good laboratory practices e.g., sterility, non-pyrogenicity, prevention of viral transfer etc. The researchers involved in the project must be properly qualified to perform the tasks required of them. While non-physicians can certainly be principal investigators in human research, they can not be allowed to perform procedures or prescribe medications. Most IRB's will accept that once precautions have been minimized as best possible, that an informed adult should be allowed to decide whether or not he or she would like to participate and accept the risks that remain.

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