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

Vaccines

Larry R. Smith²  Mary K. Wloch²  Jennifer A. Chaplin²  Michele Gerber¹ 

[1] Astellas Pharma Global Development, Inc., 1 Astellas Way, Northbrook, IL 60062, USA; E-Mail:;Vical Incorporated, 10390 Pacific Center Court, San Diego, California, CA 92121, USA; E-Mails:

关键词: 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);   

DOI  :  10.3390/vaccines1040398

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.