title: Long-lived poxvirus immunity, robust CD4 help, and better persistence of CD4 than CD8 T cells.
abstract: The currently used smallpox vaccine is associated with a high incidence of adverse events, and there is a serious need for a safe and effective alternative vaccine. Here, we carried out a longitudinal evaluation of vaccinia virus-specific CD4 and CD8 T cells in smallpox-vaccinated individuals by using a highly sensitive intracellular cytokine staining assay. Our results demonstrate that, in addition to the CD8 response, the smallpox vaccinations raised a robust CD4 response with a Th1-dominant cytokine profile. These CD4 T cells were stable and exhibited only a twofold contraction between peak effector and memory phases compared with an approximate sevenfold contraction for CD8 cells. A significant proportion of vaccinated individuals lost detectable CD8 memory while maintaining CD4 memory. After a booster immunization, these individuals generated a robust CD8 response, which some of them rapidly lost. Thus, the current smallpox vaccine provides long-lasting CD4 help that may be critical for long-lived B-cell memory. We suggest that the provision of adequate CD4 help for CD8 and humoral effector functions will be critical to the success of the next generation of smallpox vaccines.
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center and Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia 30329, USA. rama@rmy.emory.edu
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Pragati
authors.initials: P
authors.lastname: Nigam
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Vanda
authors.initials: V
authors.lastname: Bostik
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008137:Longitudinal Studies; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D012901:Variola virus / Q000276:immunology*
chemical_list: D016207:Cytokines; D012900:Smallpox Vaccine