title: Importance of antibody in virus infection and vaccine-mediated protection by a latency-deficient recombinant murine γ-herpesvirus-68.
abstract: The human γ-herpesviruses EBV and Kaposi's sarcoma-associated herpesvirus establish lifelong latent infections, can reactivate in immunocompromised individuals, and are associated with the development of malignancies. Murine γ-herpesvirus-68 (γHV68), a rodent pathogen related to EBV and Kaposi's sarcoma-associated herpesvirus, provides an important model to dissect mechanisms of immune control and investigate vaccine strategies. Infection of mice with γHV68 elicits robust antiviral immunity, and long-term protection from γHV68 reactivation requires both cellular and humoral immune responses. Vaccination of mice with AC-replication and transcription activator (RTA), a highly lytic latency-null recombinant γHV68, results in complete protection from wild-type γHV68 infection that lasts for at least 10 mo. In this report, we examine the immune correlates of AC-RTA-mediated protection and show that sterilizing immunity requires both T cells and Ab. Importantly, Ab was also critical for mitigating viral infection in the brain, and in the absence of Ab-mediated control, amplification of the AC-RTA virus in the brain resulted in fatality. Our results highlight important considerations in the development of vaccination strategies based on live-attenuated viruses.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.forename: Claire E
authors.initials: CE
authors.lastname: Burkum
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wu
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blackman
mesh_terms: D000818:Animals; D000914:Antibodies, Viral; D007109:Immunity; D051379:Mice; D008810:Mice, Inbred C57BL; D018144:Rhadinovirus; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated; D014775:Virus Activation; D014777:Virus Diseases / Q000276:immunology* / Q000517:prevention & control; D017735:Virus Latency
chemical_list: D000914:Antibodies, Viral; D014612:Vaccines; D014613:Vaccines, Attenuated