IMMUNOLOGY - Roit A. - Mir 2000

Chapter 19. Vaccination

VACCINE EFFICACY

An officially approved vaccine must be reliably efficacious, and the efficacy of all Vaccines used in clinical practice is periodically re-evaluated. The effectiveness of a vaccine is determined by numerous factors. To be considered efficacious, a vaccine must possess the following properties:

✵ to induce the appropriate form of Immune Response; for example, prompting The production of Antibodies against toxins and extracellular microbes, such as Streptococcus pneumoniae, or generating Cell-mediated Immunity against intracellularly replicating pathogens, such as Mycobacterium tuberculosis. When the optimal type of response is unknown (as in malaria), designing an effective vaccine becomes considerably more difficult;

✵ to be stable during storage; this is particularly critical for live vaccines, which must be continuously maintained at low temperatures all the way from manufacturing to the clinical Setting, a requirement that is not always easy to achieve;

✵ to possess sufficient immunogenicity; in the case of inactivated vaccines, this often needs to be enhanced by The Use of an adjuvant (see below).

Live vaccines are generally more efficacious than inactivated ones

To elicit immunity of the requisite magnitude, an antigen must possess specific properties. The advantage of live vaccines over inactivated ones lies in their ability to provide a sustained antigenic stimulus lasting over days or weeks, while establishing immunity precisely at the site where it is needed. In practice, this is especially important for inducing mucosal immunity (Fig. 19.10). Furthermore, live vaccines presumably contain the greatest diversity of microbial Antigens. Inactivated vaccines may also suffer from two drawbacks related to The Nature of the immune response they elicit: T-cell independence and Major Histocompatibility Complex (MHC) restriction (see Ch. 11 and 13). Typical T-independent antigens are Polysaccharides; they do not bind to MHC molecules and therefore fail to recruit T Cells into the response. To induce T-cell-mediated immunological memory, polysaccharides in modern vaccines are conjugated either to a standard protein carrier, such as tetanus toxoid (see below), or to one of the pathogen's own Proteins, such as an outer membrane protein from pneumococci, Haemophilus, etc. MHC restriction influences the response against short Peptides of 10–20 amino acid residues and manifests as "genetic non-responsiveness"—such peptides interact only with specific MHC molecules. While a lack of response due to MHC restriction is likely a largely hypothetical concern, given that most candidate vaccines contain significantly larger peptides, even the most efficacious vaccines frequently fail to achieve one hundred percent immunization; for instance, following a complete course of hepatitis B vaccination, lack of seroconversion is observed in approximately 5% of vaccinees.

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Fig. 19.10. Antibody production in response to oral administration of a live attenuated polio vaccine (solid lines) and intramuscular administration of an inactivated polio vaccine (dashed lines). In addition to serum IgM and IgG antibodies, the live vaccine induces the production of secretory IgA (sIgA). Because sIgA antibodies are generated within the mucosa-associated lymphoid tissue (MALT) system (see Ch. 3), the live vaccine provides antiviral protection at the portal of entry of the infection—the gastrointestinal mucosa. (Kindly provided by Prof. J.R. Pattison, from Brostoff J. et al., eds. Clinical Immunology (Ch. 26) London: Mosby, 1991.)