Smallpox Vaccines for Biodefense: Need and Feasibility

Andrew W Artenstein; John D Grabenstein

Disclosures

Expert Rev Vaccines. 2008;7(8):1225-1237. 

In This Article

Expert Commentary

First-generation smallpox vaccines have a long, distinguished track record of effectiveness in the control and subsequent eradication of naturally occurring smallpox. However, their utility in the posteradication setting is limited by uncommon but serious adverse effects ( Table 2 ). The incidence of some of the more notorious of these complications can be minimized by rigorous screening for known contraindications and site hygiene; others, such as myopericarditis, have not yet had clear precipitating factors identified. A significant proportion of the population would be excluded from receiving these vaccines in nonemergent scenarios.

New-generation smallpox vaccines, specifically second- (tissue culture-derived vaccinia) and third-generation (highly attenuated vaccinia) vaccines potentially have a similar efficacy to first-generation smallpox vaccines. Second-generation vaccines, as with first-generation ones, are associated with a significant risk of myopericarditis that substantially limits their utility in a pre-event setting. With the licensure of ACAM2000 and its substitution as the principal vaccine in the ongoing DoD program, the FDA has imposed a risk-minimization action plan that includes a myopericarditis case registry and Phase IV cohort study of military vaccinees to further characterize cardiac adverse events.[110] Third-generation products may possess improved safety profiles, but this has yet to be proven in adequately powered studies or experience with large numbers of vaccinees. Highly attenuated, replication-defective vaccinia MVA sacrifices degrees of immunogenicity and efficacy for its theoretically improved safety profile. For some third-generation products, multidose regimens limit their utility in outbreak settings.

The risk versus benefit profile of smallpox vaccination is complex ( Table 3 ). The risks associated with currently licensed vaccines probably do not justify their pre-event use in groups with a very low perceived risk of smallpox exposure. However, the latter type of risk is dependent on the unpredictable nature of terrorists and may be stratified among different groups; for example, deployed military forces may be at higher levels of exposure risk. Additionally, the general level of perceived risk may increase abruptly should a terrorist event occur. Such an unpredictable situation argues for continued research on safer smallpox vaccines. New-generation vaccines that are demonstrated to have significantly improved safety profiles after adequate human studies may alter the risk-versus-benefit assessment.

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