%0 Journal Article
%T Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial
%A Larry R. Smith
%A Mary K. Wloch
%A Jennifer A. Chaplin
%A Michele Gerber
%A Alain P. Rolland
%J Vaccines
%D 2013
%I MDPI AG
%R 10.3390/vaccines1040398
%X 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-¦Ã-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.
%K plasmid DNA vaccine
%K cytomegalovirus (CMV)
%K glycoprotein B (gB)
%K phosphoprotein 65 (pp65)
%K poloxamer CRL1005
%K benzalkonium chloride (BAK)
%K hematopoietic cell transplant (HCT)
%K CMV end organ disease (EOD)
%U http://www.mdpi.com/2076-393X/1/4/398