Neutralizing vaccination against viral interleukin-6 from a primate rhadinovirus

Herpesviruses are ancient viruses that devote a significant fraction of their protein-coding potential to interference with host immunity. Diverse herpesviruses encode proteins with similarity to host MHC molecules, interferon regulatory factors, complement regulators, G-protein coupled receptors, chemokines, and cytokines. Certain gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and rhesus rhadinovirus (RRV), encode viral cytokines similar to host IL-6, called viral IL-6 (vIL-6). The potential of vIL-6 to act as a protective vaccine antigen against these rhadinoviruses remains under-explored. We isolated a new RRV strain, which encodes virion surface proteins similar to those of previous isolates and a vIL-6 that is nearly identical. We found that, although unmodified vIL-6 is a poor immunogen eliciting low neutralizing titers, vIL-6-Fc fusion protein elicits high-titer responses after either one or two doses. We detected no adverse effects related to cytokine activity, nor interference with concomitantly administered vaccine against the RRV glycoprotein B. Our results demonstrate an approach for eliciting neutralizing antibodies against a highly conserved viral protein that contributes to rhadinovirus persistence and oncogenesis.