Vaccines 2013, 1(4), 398-414; doi:10.3390/vaccines1040398
Case Report

Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial

1,* email, 1email, 1email, 2email and 1email
Received: 10 July 2013; in revised form: 23 August 2013 / Accepted: 28 August 2013 / Published: 25 September 2013
(This article belongs to the Special Issue DNA Vaccines)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV+) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV+ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.
Keywords: plasmid DNA vaccine; cytomegalovirus (CMV); glycoprotein B (gB); phosphoprotein 65 (pp65); poloxamer CRL1005; benzalkonium chloride (BAK); hematopoietic cell transplant (HCT); CMV end organ disease (EOD)
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MDPI and ACS Style

Smith, L.R.; Wloch, M.K.; Chaplin, J.A.; Gerber, M.; Rolland, A.P. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial. Vaccines 2013, 1, 398-414.

AMA Style

Smith LR, Wloch MK, Chaplin JA, Gerber M, Rolland AP. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial. Vaccines. 2013; 1(4):398-414.

Chicago/Turabian Style

Smith, Larry R.; Wloch, Mary K.; Chaplin, Jennifer A.; Gerber, Michele; Rolland, Alain P. 2013. "Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial." Vaccines 1, no. 4: 398-414.

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