Induction of Human T Cell–Mediated Immune Responses after Primary and Secondary Smallpox Vaccination

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)-γ-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-g 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.