Immune Responses and Vaccine Development for Cytomegalovirus Infections

Abstract

Aims: (1) To review the published literature on immune biology of host-Cytomegavovirus (CMV) interactions and to discuss the host immune responses against viral infection, providing insights into the complex interplay between the host and the virus that facilitates viral persistence. (2) To report on the status of CMV vaccines that are currently in preclinical and clinical development, outlining important questions about the nature of protective immune responses that will be required of potential CMV immunization strategies. Methodology: A Pub Med search of original articles and reviews in English language only between the years 1974-2013 was conducted using “CMV infection”, “CMV vaccines”, “CMV immune responses” and “CMV clinical trials” as keywords. Inclusion criteria were a description of the CMV disease in immune compromised patients and in individuals affected by the virus through congenital transmission, clinical observations in the course of CMV infection, the overview of the host immune responses and CMV factors in the outcome of CMV infection, the current status of therapeutic strategies and vaccine development. Results: CMV is found throughout the world in all geographic and socioeconomic groups, but, in general, it is more widespread in developing countries and in areas of lower socioeconomic conditions. CMV still remains a major human pathogen causing significant morbidity and mortality in immune suppressed or immune compromised individuals. Between 50% and 80% of adults in the United States are infected with CMV by 40 years of age. CMV is the most common congenitally transmitted virus, resulting in approximately 1 in 150 children born with congenital CMV infection, and in about 1 in 750 children developing permanent disabilities due to CMV. Thus, development of vaccines against CMV infections has been a major biomedical research priority. Conclusion: There is a need for an effective CMV vaccine that will protect immune compromised transplant patients as well as newborns, although the key requirements for protection of these two populations (and the optimal vaccine strategy to provide this protection) may differ. To date, only the Towne vaccine – a live, attenuated CMV vaccine – has undergone efficacy evaluation. Application of molecular biological techniques, coupled with an improved understanding of the CMV genome, should allow design of safer, more immunogenic, live, attenuated vaccines.