Characterization of Human Anti-Cytomegalovirus Monoclonal Antibodies

Abstract

Cytomegalovirus (CMV) is a member of the herpesvirus group that infects a major fraction of the human population. Most of these individuals have little or no clinical symptoms of overt disease but commence a life-long carrier-state upon infection. Serious disease and death can result when infection occurs in immunocompromised individuals (including fetuses and neonates) or upon reactivation of latent virus if the previous infection was followed by a decline in immune function. Progression of disease to pneumonia frequently results in death because antiviral drugs have had little success in treatment at this stage. Little is known about the efficacy of pooled immunoglobulin containing high titers of anti-CMV antibodies, although there is one report of success (Blacklock et al., 1985). Because high-risk populations for serious CMV disease can be easily identified and current treatments lack proven efficacy, some effort has been invested in prophylactic treatment. Immunoglobulin preparations are ideal candidates for prophylaxis because of their low toxicity. Pooled immunoglobulin of high anti-CMV titer have had variable success (Meyers, et al., 1983; Bowden et al., 1986), possibly owing to variations in different batches of the preparation. Human monoclonal antibodies may be useful for both disease therapy and prophylaxis because they allow very high-titer standardized preparations to be injected. These characteristics may overcome the drawbacks inherent in pooled immunoglobulin preparations. In this report, we review the properties of human monoclonal antibodies directed against CMV including in vitro biochemical, immunochemical, and biological characteristics and in vivo pharmacokinetic and immunogenicity studies. The final important property of these antibodies, in vivo neutralization efficacy, remains to be proven, but clinical trials are just beginning.