Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

Slobodan Paessler, Nadezhda E. Yun, Barbara M. Judy, Natallia Dziuba, Michele A. Zacks, Anna H. Grund, Ilya Frolov, Gerald A. Campbell, Scott C. Weaver, D. Mark Estes

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3+ T cells are required for protection.

Original languageEnglish (US)
Pages (from-to)307-323
Number of pages17
JournalVirology
Volume367
Issue number2
DOIs
StatePublished - Oct 25 2007

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Keywords

  • Alphavirus immunity
  • Pathogenesis
  • Recombinant vaccines
  • Venezuelan equine encephalitis virus

ASJC Scopus subject areas

  • Virology

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