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

Journal Article · Thu Oct 25 00:00:00 EDT 2007 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.05.041· OSTI ID:21077983

Paessler, Slobodan ^[1]; Yun, Nadezhda E ^[1]; Judy, Barbara M ^[2]; Dziuba, Natallia; Zacks, Michele A; Grund, Anna H ^[1]; Frolov, Ilya ^[3]; Campbell, Gerald A; Weaver, Scott C ^[1]; Estes, D Mark ^[1]

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1. Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609 (United States)
2. Sealy Center for Vaccine Development, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0372 (United States)
3. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019 (United States)

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{sup +} T cells are required for protection.

• OSTI ID: 21077983
• Journal Information: Virology, Vol. 367, Issue 2; Other Information: DOI: 10.1016/j.virol.2007.05.041; PII: S0042-6822(07)00403-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
BRAIN
ENCEPHALITIS
IMMUNITY
IMMUNOGLOBULINS
INTERFERON
MICE
PATHOGENESIS
RECEPTORS
VACCINES
VIRUSES