Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination
Department of Medicine, Division of Infectious Diseases and Immunology; Center for Infectious Disease and Vaccine Research
Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease
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.
DOI of Published Version
J Infect Dis. 2004 Oct 1;190(7):1286-94. Epub 2004 Aug 30. doi:10.1086/423848 Link to article on publisher's site
The Journal of infectious diseases
Kennedy, Jeffrey S.; Frey, Sharon E.; Yan, Lihan; Rothman, Alan L.; Cruz, John; Newman, Frances K.; Orphin, Laura; Belshe, Robert B.; and Ennis, Francis A., "Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination" (2004). Infectious Diseases and Immunology Publications and Presentations. 267.