title: Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection.
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 (alphabeta) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (gammadelta) 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 (microMT) 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.
authors.affiliation: Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA. slpaessl@utmb.edu
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Yun
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Judy
authors.forename: Natallia
authors.initials: N
authors.lastname: Dziuba
authors.forename: Michele A
authors.initials: MA
authors.lastname: Zacks
authors.forename: Anna H
authors.initials: AH
authors.lastname: Grund
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Campbell
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D012449:Safety; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D014613:Vaccines, Attenuated; D014765:Viral Vaccines