Designing Vaccines for Active Immunization

The Revised Authoritative Guide To Vaccine Legal Exemptions

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Several factors must be kept in mind in developing a successful vaccine. First and foremost, the development of an immune response does not necessarily mean that a state of protective immunity has been achieved. What is often critical is which branch of the immune system is activated, and therefore vaccine designers must recognize the important differences between activation of the humoral and the cellmediated branches. A second factor is the development of immunologic memory. For example, a vaccine that induces a protective primary response may fail to induce the formation of memory cells, leaving the host unprotected after the primary response to the vaccine subsides.

The role of memory cells in immunity depends, in part, on the incubation period of the pathogen. In the case of influenza virus, which has a very short incubation period (1 or 2 days), disease symptoms are already under way by the time memory cells are activated. Effective protection against influenza therefore depends on maintaining high levels of neutralizing antibody by repeated immunizations; those at highest risk are immunized each year. For pathogens with a longer incubation period, maintaining detectable neutralizing antibody at the time of infection is not necessary. The poliovirus, for example, requires more than 3 days to begin to infect the central nervous system. An incubation period of this length gives the memory B cells time to respond by producing high levels of serum antibody. Thus, the vaccine for polio is designed to induce high levels of immunologic memory. After immunization with the Salk vaccine, serum antibody levels peak within 2 weeks and then decline, but the memory response continues to climb, reaching maximal levels at 6 months and persisting for years (Figure 18-3). If an immunized individual is later exposed to the poliovirus, these memory cells will respond by differentiating into plasma cells that produce high levels of serum antibody, which defend the individual from the infection.

In the remainder of this chapter, various approaches to the design of vaccines—both currently used vaccines and experimental ones—are described, with an examination of their ability to induce humoral and cell-mediated immunity and the production of memory cells.

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Vaccine

FIGURE 18-3

Antibody Mediated Resonse Polio

Time, months

Immunization with a single dose of the Salk polio vaccine induces a rapid increase in serum antibody levels, which peak by 2 weeks and then decline. Induction of immunologic memory follows a slower time course, reaching maximal levels 6 months after vaccination. The persistence of the memory response for years after primary vaccination is responsible for immunity to poliomyelitis. [From M. Zanetti et al, 1987, Immunol. Today 8:18.]

Time, months

Immunization with a single dose of the Salk polio vaccine induces a rapid increase in serum antibody levels, which peak by 2 weeks and then decline. Induction of immunologic memory follows a slower time course, reaching maximal levels 6 months after vaccination. The persistence of the memory response for years after primary vaccination is responsible for immunity to poliomyelitis. [From M. Zanetti et al, 1987, Immunol. Today 8:18.]

Classification of common vaccines for humans

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