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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,* , 1
,
1
,
2
 and
1
1 Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA 2 Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL 60062, USA
* Author to whom correspondence should be addressed.
Received: 10 July 2013 / Revised: 23 August 2013 / Accepted: 28 August 2013 / Published: 25 September 2013
(This article belongs to the Special Issue DNA Vaccines)
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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) 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)
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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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.

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