Correlations between vaccinia-specific immune responses within a cohort of armed forces members

Benjamin J. Umlauf, Inna G. Ovsyannikova, Iana H. Haralambieva, Richard B. Kennedy, Robert A. Vierkant, V. Shane Pankratz, Robert M. Jacobson, Gregory A. Poland

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 ®. We measured multiple VACV-specific immune responses: neutralizing antibody titer, the level of 12 secreted cytokines in peripheral blood mononuclear cell (PBMC) cultures (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, TNF-α, IFN-γ, IFN-α, IFN-β, and IL-18), and the number of IFN-γ-and CD8 + IFN-γ-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 15.3mo following primary vaccination. We also detected correlations between neutralizing antibody titer and secreted IL-2, as well as secreted IFN-γ (p=0.009 and p=0.0007, respectively). We also detected strong correlations between the proinflammatory cytokines IL-1β, TNF-α, 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.

Original languageEnglish (US)
Pages (from-to)415-420
Number of pages6
JournalViral Immunology
Volume24
Issue number5
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

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