Vaccine prospect of Kaposi sarcoma-associated herpesvirus

Infection of Kaposi sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) is estimated to account for 34,000 new cancer cases globally. Unlike other herpesviruses, KSHV is not ubiquitous but is highly prevalent in some areas, such as sub-Saharan Africa where Kaposi sarcoma is the leading cancer among adults. While latent infection of KSHV plays a major and direct role in tumorigenesis, viral lytic replication also makes significant contributions to this process. Efforts to develop a KSHV vaccine are limited, but studies with EBV have provided important lessons. Informative vaccine research has been conducted in the mouse infection model of a closely related rodent virus, murine gammaherpesvirus-68 (MHV-68 or γHV-68). This mouse model has generated fundamental principles for an effective vaccination strategy. KSHV vaccines designed to prevent a naïve host from infection and to boost the immune control of KSHV in persistently infected people will have major impact on individuals who are at a high risk of developing KSHV-associated diseases.

► Life-long infection of KSHV is associated with tumorigenesis, and latency and lytic replication contribute to KSHV pathogenesis. ► About 90% of KSHV occurs in sub-Saharan Africa where it is endemic and primarily transmitted via non-sexual contacts. ► Vaccines against KSHV provide an affordable opportunity to reduce cancer burden, especially in resource-limited areas. ► In the MHV-68 mouse infection model, subunit or killed virus vaccine does not impact long-term latency. ► The only effective vaccination strategy that can protect against latent infection is based on live attenuated viruses.