Immune Prophylaxis and Therapy for Human Cytomegalovirus Infection

Abstract

Human Cytomegalovirus (HCMV) infection is widespread and can result in severe sequelae in susceptible populations. Primary HCMV infection of naïve individuals results in life-long latency characterized by frequent and sporadic reactivations. HCMV infection elicits a robust antibody response, including neutralizing antibodies that can block the infection of susceptible cells in vitro and in vivo. Thus, antibody products and vaccines hold great promise for the prevention and treatment of HCMV, but to date, most attempts to demonstrate their safety and efficacy in clinical trials have been unsuccessful. In this review we summarize publicly available data on these products and highlight new developments and approaches that could assist in successful translation of HCMV immunotherapies.

An Overview of Cytomegalovirus Infection in Pregnancy

“…When the maternal infection has been diagnosed periconceptionally, in the first trimester, or in the early second trimester, the risk of fetal infection and disease can be decreased by administering hyperimmunoglobulin [ 80 ]. Studies report that high-avidity immunoglobins administered to a seropositive patient decrease the risk of fetal infection from 40% to 16% and from 44% to 30%, respectively [ 80 , 81 ]. Others reported a transmission rate of 23% in the presence of specific treatments.…”

“…The administration of hyperimmunoglobulin in the first 20 weeks of gestation is considered beneficial, particularly in CMV primary infections, having demonstrated a decrease in fetal disease cases in terms of infection and clinical abnormalities. After 20 weeks of gestation, there is no consensus on the benefit of treatment administration [ 81 , 82 ].…”

Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation

“…Receptor binding to Trimer and Pentamer complexes is thought to trigger the irreversible transition of gB from a metastable prefusion conformation to a highly stable postfusion conformation, thereby facilitating fusion of the viral and host-cell membranes. Given its essential role in viral entry, gB is typically included in HCMV vaccine candidate formulations ( 15 ). Of the vaccine candidates tested in humans, recombinant gB delivered with the MF59 adjuvant has shown promise in phase II clinical trials (NCT00125502, NCT00133497), achieving 40– 50% short-lived efficacy in preventing HCMV infection in both adolescent and postpartum cohorts ( 16, 17 ), as well as reducing viremia and antiviral prophylaxis in renal transplant patients ( 18 ).…”

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

“…As a result, there is a great need for the development of alternative treatment options against HCMV [4,5]. In this regard, immunotherapy has emerged as a promising strategy to overcome the side effects of antiviral treatment and for the development of prophylaxis measures [6][7][8]. Particularly, Thymosin-alpha-1 (Tα1) has been shown to play a key role in the control of immunity, tolerance and inflammation, which explains its wide range of clinical applications in several pathologies, including infectious diseases [9].…”