Thursday, November 18, 2010

SAFETY AND IMMUNOGENICITY OF A BIVALENT CMV DNA VACCINE IN HEALTHY ADULT SUBJECTS

Background

VCL-CB01, a candidate CMV DNA vaccine containing plasmids encoding CMV phosphoprotein 65 (pp65) and glycoprotein B (gB) to induce cellular and humoral immune responses and formulated with poloxamer CRL1005 and benzalkonium chloride to enhance immune responses, was evaluated in a Phase 1 clinical trial.

Methods

VCL-CB01 was evaluated in 44 healthy adult subjects (22 CMV-seronegative, 22 CMV-seropositive) ages 18-43. Thirty-two subjects received 1 mg or 5 mg doses of vaccine on a 0-, 2-, and 8-week schedule, and 12 subjects received 5 mg doses of vaccine on a 0-, 3-, 7-, and 28-day schedule.

Results

Overall, the vaccine was well tolerated with no serious adverse events. Local reactions included mild to moderate injection site pain and tenderness, induration, and erythema. Systemic reactions included mild to moderate malaise and myalgia. All reactions resolved without sequelae. Through Week 16 of the study, immunogenicity, as measured by ELISA and/or ex vivo IFN-γ ELISPOT assay, was documented in 45% of CMV-seronegative subjects and 25% of CMV-seropositive subjects who received the full vaccine series and 68% of CMV-seronegative subjects had memory IFN-γ T-cell responses at Week 32.

Conclusion

The safety and immunogenicity data from this trial support further evaluation of VCL-CB01. Keywords: DNA vaccine, cytomegalovirus, clinical trial, hematopoietic cell transplant, congenital CMV

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