Immunotherapeutic Approaches To Prevent Cytomegalovirus-Mediated Disease

Human cytomegalovirus (CMV) is the major cause of congenital neurological defects in the United States and also causes significant morbidity and mortality for hematopoietic and solid organ transplant patients. Primary infection in immunocompetent individuals rarely causes disease but resolves as a life-long latent infection, characterized by sustained antibody and cellular responses. Despite considerable efforts over the last 40 years to develop live attenuated and subunit vaccines, none is close to receiving regulatory approval. However, there is evidence that antibodies can prevent primary infection and cytotoxic T cells can suppress secondary infection. Prior maternal infection decreases the risk a fetus will contract CMV, while adoptive transfer of virus-specific CD8+ T cells is highly protective against CMV disease in hematopoietic stem cell transplant recipients. As a result, three polyclonal immunoglobulin preparations are approved for clinical use and one monoclonal antibody has reached phase III trials. Enhanced understanding of the viral life cycle from a biochemical perspective has revealed additional targets for neutralizing antibodies in the gH/gL/UL128-131 pentamer. Until an effective vaccine is licensed, passive immunotherapeutics may present an alternative to maintain viral loads and prevent CMV disease in susceptible populations. This review summarizes the progress and potential of immunotherapeutics to treat CMV infection.