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

作者:Paessler Slobodan*; Yun Nadezhda E; Judy Barbara M; Dziuba Natallia; Zacks Michele A; Grund Anna H; Frolov Ilya; Campbell Gerald A; Weaver Scott C; Estes D Mark
来源:Virology, 2007, 367(2): 307-323.
DOI:10.1016/j.virol.2007.05.041

摘要

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 (alpha beta) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (gamma delta) 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 (mu MT) 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.

  • 出版日期2007-10-25