Progress toward an elusive goal: current status of cytomegalovirus vaccines

Although infection with human cytomegalovirus (CMV) is ubiquitous and generally asymptomatic in most individuals, certain patient populations are at high risk for CMV-associated disease. These include HIV-infected individuals with AIDS, transplant patients, and newborn infants with congenital CMV infection. Immunity to CMV infection, both in the transplant setting and among women of childbearing age, plays a vital role in the control of CMV-induced injury and disease. Although immunity induced by CMV infection is not completely protective against reinfection, there is nevertheless a sound basis on which to believe that vaccination could help control CMV disease in high-risk patient populations. Evidence from several animal models of CMV infection indicates that a variety of vaccine strategies are capable of inducing immune responses sufficient to protect against CMV-associated illness following viral challenge. Vaccination has also proven effective in improving pregnancy outcomes following CMV challenge of pregnant guinea pigs, providing a 'proof-of-principle' relevant to human clinical trials of CMV vaccines. Although there are no licensed vaccines currently available for human CMV, progress toward this goal has been made, as evidenced by ongoing clinical trial testing of a number of immunization strategies. CMV vaccines currently in various stages of preclinical and clinical testing include: protein subunit vaccines; DNA vaccines; vectored vaccines using viral vectors, such as attenuated pox- and alphaviruses; peptide vaccines; and live attenuated vaccines. This review summarizes some of the obstacles that must be overcome in development of a CMV vaccine, and provides an overview of the current state of preclinical and clinical trial evaluation of vaccines for this important public health problem.