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Duration of antiviral immunity after smallpox vaccination


Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25–75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1–75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8–15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.

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Figure 1: Virus-specific CD4+ T-cell memory after smallpox vaccination.
Figure 2: Virus-specific CD8+ T-cell memory after smallpox vaccination.
Figure 3: Relationship between vaccinia-specific CD4+ and CD8+ T-cell memory over time.
Figure 4: Long-lived antiviral antibody responses induced by smallpox vaccination.


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We thank the many volunteers for the generous gift of their time and their unselfish participation in this research study; S. Tofte, T. Gromlich and K. Buxton for technical assistance; J. Kravitz, A. Melnick and G. Oxman for their support; and J.L. Whitton for insightful discussions. This work was supported by Oregon Health and Science University postdoctoral fellowship T32HL07781 (to S.G.H.), National Institutes of Health grants AI21640 (to J.A.N.) and AI051346 (to M.K.S.), Public Health Service grant 5 M01 RR00334 (to M.K.S.) and Oregon National Primate Research Center grant RR00163 (to M.K.S.).

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Correspondence to Mark K Slifka.

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Hammarlund, E., Lewis, M., Hansen, S. et al. Duration of antiviral immunity after smallpox vaccination. Nat Med 9, 1131–1137 (2003).

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