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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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.
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.
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.