PMID- 21958369 OWN - NLM STAT- MEDLINE DCOM- 20120208 LR - 20211020 IS - 1557-8976 (Electronic) IS - 0882-8245 (Print) IS - 0882-8245 (Linking) VI - 24 IP - 5 DP - 2011 Oct TI - Correlations between vaccinia-specific immune responses within a cohort of armed forces members. PG - 415-20 LID - 10.1089/vim.2011.0029 [doi] AB - Widespread vaccination with vaccinia virus (VACV) resulted in the eradication of smallpox; however, the licensed VACV-containing vaccines are associated with adverse events (AEs), making them unsuitable for certain high-risk populations. A better understanding of the host immune response following smallpox vaccination could result in vaccines with similar immunogenicity profiles to pre-eradication vaccines with a lower incidence of AEs. To study the immune response to VACV, we recruited 1,076 armed forces members who had been vaccinated with one dose of Dryvax((R)). We measured multiple VACV-specific immune responses: neutralizing antibody titer, the level of 12 secreted cytokines in peripheral blood mononuclear cell (PBMC) cultures (IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, TNF-alpha, IFN-gamma, IFN-alpha, IFN-beta, and IL-18), and the number of IFN-gamma- and CD8(+) IFN-gamma-secreting cells. We analyzed these data to determine correlations between immune response measures. We detected a strong proinflammatory response in concert with a Th-1-like cytokine response pattern at a median time point of 15.3 mo following primary vaccination. We also detected correlations between neutralizing antibody titer and secreted IL-2, as well as secreted IFN-gamma (p=0.009 and p=0.0007, respectively). We also detected strong correlations between the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, and IL-12p40 (p<0.0001). These results further advance our knowledge of vaccinia-specific cellular immune responses. Notably, vaccine-induced proinflammatory responses were not correlated with neutralizing antibody titers, suggesting that further attenuation to reduce inflammatory immune responses may result in decreased AEs without sacrificing VACV immunogenicity and population seropositivity. FAU - Umlauf, Benjamin J AU - Umlauf BJ AD - Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA. FAU - Ovsyannikova, Inna G AU - Ovsyannikova IG FAU - Haralambieva, Iana H AU - Haralambieva IH FAU - Kennedy, Richard B AU - Kennedy RB FAU - Vierkant, Robert A AU - Vierkant RA FAU - Pankratz, V Shane AU - Pankratz VS FAU - Jacobson, Robert M AU - Jacobson RM FAU - Poland, Gregory A AU - Poland GA LA - eng GR - AI-40065/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110929 PL - United States TA - Viral Immunol JT - Viral immunology JID - 8801552 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Cytokines) RN - 0 (DryVax vaccine) RN - 0 (Smallpox Vaccine) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adolescent MH - Adult MH - Antibodies, Neutralizing/*blood MH - Antibodies, Viral/blood MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cohort Studies MH - Cytokines/blood MH - Female MH - Humans MH - Immunity, Cellular/*immunology MH - Interferon-gamma/biosynthesis MH - Male MH - *Military Personnel MH - Smallpox Vaccine/administration & dosage/*immunology MH - Th2 Cells/immunology MH - Vaccination MH - Vaccinia/*immunology/prevention & control/virology MH - Vaccinia virus/*immunology MH - Young Adult PMC - PMC3236101 EDAT- 2011/10/01 06:00 MHDA- 2012/02/09 06:00 PMCR- 2012/10/01 CRDT- 2011/10/01 06:00 PHST- 2011/10/01 06:00 [entrez] PHST- 2011/10/01 06:00 [pubmed] PHST- 2012/02/09 06:00 [medline] PHST- 2012/10/01 00:00 [pmc-release] AID - 10.1089/vim.2011.0029 [pii] AID - 10.1089/vim.2011.0029 [doi] PST - ppublish SO - Viral Immunol. 2011 Oct;24(5):415-20. doi: 10.1089/vim.2011.0029. Epub 2011 Sep 29.