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.