Can we build it better? Using BAC genetics to engineer more effective cytomegalovirus vaccines

Abstract

The magnitude and durability of immunity to human cytomegalovirus (HCMV) following natural infection is compromised by the presence of immune modulation genes that appear to promote evasion of host clearance mechanisms. Since immunity to HCMV offers limited protection, rational design of effective vaccines has been challenging. In this issue of the JCI, Slavuljica and colleagues employ techniques to genetically modify the highly related mouse CMV (MCMV), in the process generating a virus that was rapidly cleared by NK cells. The virus functioned as a safe and highly effective vaccine. Demonstration of the ability to engineer a safe and highly effective live virus vaccine in a relevant rodent model of CMV infection may open the door to clinical trials of safer and more immunogenic HCMV vaccines.

Could Therapeutic Vaccination of Cytomegalovirus-Seropositive Persons Prevent Reinfection and Congenital Virus Transmission?

“…Or, in a broader sense, can the viral and host factors that contribute to the suboptimal immune response to CMV be elucidated, toward the goal of designing more effective live virus vaccines that protect against both primary infection and reinfection? It is conceivable that this goal might be achieved by deletion of viral immune evasion genes from a live virus vaccine candidate, and there is evidence from animal models of CMV infection that this is feasible [35,36]. Until such live vaccines pass the safety hurdles required for phase I studies, trials of gB/MF59 in CMV-seropositives should continue.…”