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 journalArticlepeer-review

56 Scopus citations


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
Issue number2
StatePublished - Oct 25 2007


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

ASJC Scopus subject areas

  • Virology


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