common usage. Experience has shown that not every vaccine candidate that was successful in laboratory and animal studies prevents disease in humans. Some potential vaccines cause unacceptable side effects, and some may even worsen the disease they were meant to prevent. Live virus vaccines pose a special threat to those with primary or acquired immunodeficiency (see Chapter 19). Stringent testing is an absolute necessity, because vaccines will be given to large numbers of well persons. Adverse side effects, even those that occur at very low frequency, must be balanced against the potential benefit of protection by the vaccine.
Vaccine development begins with basic research. Recent advances in immunology and molecular biology have led to effective new vaccines and to promising strategies for finding new vaccine candidates. Knowledge of the differences in epi-topes recognized by T cells and B cells has enabled immunol-ogists to begin to design vaccine candidates to maximize activation of both arms of the immune system. As differences in antigen-processing pathways became evident, scientists began to design vaccines and to use adjuvants that maximize antigen presentation with class I or class II MHC molecules.
Vaccination: Challenges in the U.S. and Developing Countries
Many previously common childhood diseases are seldom seen in the United States, a testament to the effectiveness of vaccination. A major barrier to similar success in the rest of the world is the difficulty of delivering vaccines to all children. However, even at home the U.S. is becoming a victim of its own success. Some parents who have never encountered diseases now nearly vanquished in the U.S. do not consider it important to have their infants vaccinated or they may be lax in adhering to recommended schedules of immunization. Others hold the uninformed belief that the risks associated with vaccination outweigh the risk of infection. This flawed reasoning is fueled by periodic allegations of linkage between vaccination and various disorders, such as the report circulating recently of a causal relationship between vaccination and autism, a condition of unknown etiology. Most such reports are based solely on the coincidental timing of vaccination and onset of disease, or on limited sampling and poor statistical analyses. So far, no alleged associations have withstood scrutiny that included large population samples and acceptable statistical methods.
While children in this country are protected against a variety of once-deadly diseases, this protection depends on continuation of our immunization programs. Dependency on herd immunity is dangerous for both the individual and society. Adverse reactions to vaccines must be examined thoroughly, of course, and if a vaccine causes unacceptable side reactions, the vaccination program must be reconsidered. At the same time, anecdotal reports of disease brought on by vaccines, and unsupported beliefs, such as the contention that vaccines weaken the immune system, must be countered by correct information from trusted sources. To retreat from our progress in immunization by noncom-pliance will return us to the age when measles, mumps, whooping cough, and polio were part of the risk of growing up.
Children in the developing world suffer from a problem different from those in the United States. Examination of infant deaths worldwide shows that existing vaccines could save the lives of millions of children. As seen in the table, there are safe, effective vaccines for five of the top ten killers of children. Although the list of diseases in the table includes HIV, TB, and malaria, for which no vaccines are available, administration of the vaccines that are recommended for infants in the United States could cut child mortality in the world by approximately half.
What barriers exist to the achievement of worldwide vaccination and complete eradication of many childhood diseases? The inability to achieve higher levels of
Genetic engineering techniques can be used to develop vaccines to maximize the immune response to selected epitopes and to simplify delivery of the vaccines. This chapter describes the vaccines now in use and describes vaccine strategies, including experimental designs that may lead to the vaccines of the future.
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