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Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination.

2004 Oct 01

Journal Article

Kennedy, J.S.; Frey, S.E.; Yan, L.; Rothman, A.L.; Cruz, J.; Newman, F.K.; Orphin, L.; Belshe, R.B.; Ennis, F.A.

J Infect Dis






Adult; Antibodies, Viral; Humans; Immunization, Secondary; Immunologic Memory; Interferon-gamma; Lymphocyte Activation; Middle Aged; Smallpox Vaccine; T-Lymphocytes, Cytotoxic; Vaccination; Vaccinia virus

BACKGROUND: Postexposure vaccination strategies rely on a rapid induction of poxvirus-specific immune responses. Postvaccination cell-mediated immune (CMI) responses have not been compared by use of controlled trials in previously vaccinated (vaccinia-nonnaive) and nonvaccinated (vaccinia-naive) individuals.METHODS: To assess the time course of vaccinia-specific CMI responses, 20 previously vaccinated and 10 vaccinia-naive individuals were vaccinated with Dryvax, and serial blood samples were drawn.RESULTS: Both groups developed peak levels of vaccinia-specific interferon (IFN)- gamma -producing T cells by day 14 after vaccination. In vaccinia-nonnaive individuals, vaccinia-specific CMI responses were detected by day 7 after vaccination and preceded the increase in antibody titers. IFN- gamma enzyme-linked immunospot responses were significantly different between the 2 groups on days 7 (greater in vaccinia-nonnaive than in vaccinia-naive individuals) and 14 (greater in vaccinia-naive than in vaccinia-nonnaive individuals). Lymphoproliferation responses in vaccinia-nonnaive individuals were significantly higher on days 3 and 7, but cytotoxic T cell lysis activity was not statistically different at any time point. Antibody responses conformed to expected primary and secondary patterns of induction.CONCLUSIONS: This study demonstrates that the kinetics of CMI responses are different after primary vaccination versus after revaccination and indicates that memory can exist in individuals vaccinated >/=30 years ago. These data support the epidemiological observation in smallpox outbreaks that successful revaccination within 4 days of exposure is partially protective. In vaccinia-nonnaive individuals, protection against smallpox during the postexposure revaccination period may require T cell memory as an essential component for the rapid induction of protective cellular and humoral responses.

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