Human cytomegalovirus vaccine development: Immune responses to look into vaccine strategy

Human cytomegalovirus (HCMV) causes considerable morbidity and disability in high risk, immunocompromised populations including recipients of solid organ transplants, and fetuses whose immune systems are not yet mature. Vaccines aimed at ameliorating the severity of disease and preventing HCMV infection can be categorized into two main approaches of vaccine design, with one focusing on virus modification and the other on individual antigens. However, no candidates in either class have been successful in achieving durable and protective immunity. Recent studies on the natural immune response provide new insight into HCMV vaccine strategy. In particular, studies have demonstrated that the incorporation of a pentameric complex is necessary for a vaccine to generate the potent neutralizing antibodies often seen in seropositive individuals. This review summarizes recent findings in the development of HCMV vaccines and key considerations that should be taken into vaccine design based on improved understanding of natural HCMV immunity.