Vaccine therapy for cytomegalovirus in the setting of allogeneic hematopoietic cell transplantation

Abstract

Passive immunization against CMV is desirable to minimize or perhaps eliminate complications related to CMV disease. In allogeneic hematopoietic cell transplantation (allo-HCT), the major challenge facing a successful anti-CMV vaccine is inducing immunity in an immunocompromised host. To date, only one CMV vaccine, ASP0113, has been evaluated in a randomized, placebo-controlled Phase II study. ASP0113 is a bivalent product containing two plasmids that encode CMV glycoprotein B and tegument phosphoprotein 65, respectively. Although there was no significant difference in rate of initiation of anti-CMV therapy, rates of CMV viremia were lower in the ASP0113 group when measured by a central laboratory. Also, time-to-first episode of viremia was longer in subjects receiving ASP0113. These findings paved the way for an ongoing placebo-controlled Phase III study aiming at enrolling 500 subjects. Results of this Phase III trial, especially if it meets clinically meaningful endpoints, will ultimately determine the role of anti-CMV vaccine strategies in allo-HCT.

Keywords:

• allogeneic hematopoietic cell transplantation
• cytomegalovirus
• vaccine

Financial & competing interests disclosure

MA Kharfan-Dabaja participated in Phase II clinical trials as a coinvestigator. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• CMV end-organ disease remains a major cause of morbidity and mortality after allo-HCT.

• Although significant advances have been made in prevention and treatment strategies of CMV infection, there remains an unmet medical need for CMV control in seropositive recipients who unfortunately suffer from either treatment-related toxicities or deadly end-organ disease.

• An immunomodulatory approach such as vaccination to tackle post-transplant viremia has now come to realization and the first encouraging Phase II study evaluating ASP0113 certainly provides the proof of concept and also opens a new era of immunotherapy for CMV treatment.

• Realization of the immunologic significance of the pentameric complex may shift vaccine targets currently in development.

• Strategies to overcome CMVs ability to evade NKG2D-mediated immune response may need to be considered for improved vaccine efficacy as well.

• The encouraging results observed with recently conducted clinical trials evaluating ASP0113 in the allo-HCT setting are noteworthy and provides new impetus to the incorporation of CMV vaccine in this population.