A fifty-year odyssey: prospects for a cytomegalovirus vaccine in transplant and congenital infection

ABSTRACT

Introduction: It has been almost fifty years since the Towne strain was used by Plotkin and collaborators as the first vaccine candidate for cytomegalovirus (CMV). While that approach showed partial efficacy, there have been a multitude of challenges to improve on the promise of a CMV vaccine. Efforts have been dichotomized into a therapeutic vaccine for patients with CMV-infected allografts, either stem cells or solid organ, and a prophylactic vaccine for congenital infection.

Areas covered: This review will evaluate research prospects for a therapeutic vaccine for transplant recipients that recognizes CMV utilizing primarily T cell responses. Similarly, we will provide an extensive discussion on attempts to develop a vaccine to prevent the manifestations of congenital infection, based on eliciting a humoral anti-CMV protective response. The review will also describe newer developments that have upended the efforts toward such a vaccine through the discovery of a second pathway of CMV infection that utilizes an alternative receptor for entry using a series of antigens that have been determined to be important for prevention of infection.

Expert commentary: There is a concerted effort to unify separate therapeutic and prophylactic vaccine strategies into a single delivery agent that would be effective for both transplant-related and congenital infection.

KEYWORDS:

• Antivirals
• cytomegalovirus
• ganciclovir
• immune response
• letermovir
• solid organ transplant
• congenital infection
• stem cell transplant
• subunit vaccine
• viral vector

Declaration of interest

D J Diamond works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA and is the Chair of the Scientific Advisory Board of Helocyte, Inc. from which he receives royalties and research funding from a sponsored research agreement. C La Rosa works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA and receives research funding from a sponsored research agreement from Helocyte, Inc. F Chiuppesi works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA and receives royalties and research funding from a sponsored research agreement from Helocyte, Inc. H Contreras works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA and receives research funding from a sponsored research agreement from Helocyte, Inc. S Dadwal works at the Department of Medical Specialties, City of Hope National Medical Center, Duarte, CA, USA and is a Merck consultant, Advisory Board member, speaker, and receives research funds; and is a SHIRE Investigator. F Wussow works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA and receives royalties and research funding from a sponsored research agreement from Helocyte, Inc.. S Bautista works at the Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA. R Nakamura works at the Department of Hematology, City of Hope National Medical Center, Duarte, CA and is a member of the Merck Scientific Advisory Board. J A Zaia works at the Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute, City of Hope, Duarte, CA and declares a financial conflict of interest with Vical INC/Astellas Biotherapeutics. The authors have no other 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

The manuscript was not funded.