Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination.
2004 Oct 01
Journal Article
Authors:
Kennedy, J.S.;
Frey, S.E.;
Yan, L.;
Rothman, A.L.;
Cruz, J.;
Newman, F.K.;
Orphin, L.;
Belshe, R.B.;
Ennis, F.A.
Secondary:
J Infect Dis
Volume:
190
Pagination:
1286-94
Issue:
7
PMID:
15346340
DOI:
10.1086/423848
Keywords:
Adult; Antibodies, Viral; Humans; Immunization, Secondary; Immunologic Memory; Interferon-gamma; Lymphocyte Activation; Middle Aged; Smallpox Vaccine; T-Lymphocytes, Cytotoxic; Vaccination; Vaccinia virus
Abstract:
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.
