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

Academic Article

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. © 2007 Elsevier Inc. All rights reserved.
  • Published In

  • Virology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Paessler S; Yun NE; Judy BM; Dziuba N; Zacks MA; Grund AH; Frolov I; Campbell GA; Weaver SC; Estes DM
  • Start Page

  • 307
  • End Page

  • 323
  • Volume

  • 367
  • Issue

  • 2