Immune responses to infectious agents usually involve antibodies directed at multiple epitopes, and only some of these antibodies, if any, confer protection. The particular T-cell epitopes recognized can also affect the nature of the response. In Section 10-2, we described linked recognition, in which antigen-specific B cells and T cells provide mutually activating signals, leading to affinity maturation and isotype switching that may be required for neutralization. This process requires that an appropriate peptide epitope for T cells be presented by the B cells, and typically that the T-cell epitope be contained within the region of protein epitope recognized by the B cell, a fact that must be considered in modern vaccine design. Indeed, the predominant epitope recognized by T cells after vaccination with respiratory syncytial virus induces a vigorous inflammatory response but fails to elicit neutralizing antibodies and thus causes pathology without protection.
16-22 Effective vaccines must induce long-lasting protection while being safe and inexpensive.
A successful vaccine must possess several features in addition to its ability to provoke a protective immune response (Fig. 16.23). First, it must be safe. Vaccines must be given to huge numbers of people, relatively few of whom are likely to die of, or sometimes even catch, the disease that the vaccine is designed to prevent. This means that even a low level of toxicity is unacceptable. Second, the vaccine must be able to produce protective immunity in a very high proportion of the people to whom it is given. Third, particularly in poorer countries where it is impracticable to give regular ‘booster’ vaccinations to dispersed rural populations, a successful vaccine must generate long-lived immunological memory. This means that the vaccine must prime both B and T lymphocytes. Fourth, vaccines must be very cheap if they are to be administered to large populations. Vaccines are one of the most cost-effective measures in health care, but this benefit is eroded as the cost per dose rises.
Another benefit of an effective vaccination program is the ‘herd immunity’ that it confers on the general population. By lowering the number of susceptible members of a population, vaccination decreases the natural reservoir of infected individuals in that population and so reduces the probability of transmission of infection. Thus, even unvaccinated members will be protected because their individual chance of encountering the pathogen is decreased. However, the herd immunity effect is seen only at relatively high levels of vaccination within a population; for mumps, the necessary level is estimated to be around 80%, and below this level sporadic epidemics can occur. This is illustrated by a marked increase in mumps in the United Kingdom in 2004-2005 in young adults as a result of the variable use in the mid-1990s of a measles/ rubella vaccine rather than the combined MMR, as the combined vaccine was in short supply at that time.
16-23 Live-attenuated viral vaccines are usually more potent than ‘killed’ vaccines and can be made safer by the use of recombinant DNA technology.