Progress on human cytomegalovirus vaccines for prevention of congenital infection and disease

•An effective vaccine for prevention of congenital CMV infection is of high medical significance.•Previous candidates of modified virus vaccines or individual antigen vaccines were of moderate efficacy.•A pentameric gH complex is missing in vaccine composition in all previous candidates.•This pentameric complex is the key antigen for potent neutralizing antibodies.•Implications of this complex in CMV vaccine design are reviewed.

Congenital infection of human cytomegalovirus (CMV) is the leading cause of childhood hearing loss and mental retardation. Unfortunately, a preventive vaccine remains elusive. Two strategies have been employed to develop CMV vaccines, including (1) attenuating CMV to generate modified virus vaccines (MVVs) or (2) isolating subunit viral antigen(s) to create individual antigen vaccines (IAVs). The most studied candidate in each category is live attenuated Towne virus and recombinant gB/MF59 vaccine, respectively. Although both were moderately efficacious, neither could induce the durable, robust humoral and cellular immunity commonly seen in CMV seropositive subjects. In addition, both vaccines failed to generate neutralizing antibodies against viral infection of endothelial, epithelial cells and leukocytes. This review discusses the virological basis of CMV tropism and its implications for vaccine design. We also highlight some recent key discoveries that may lead to the development of an effective CMV vaccine.