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Clinical Trial
. 2008 Jun 15;197(12):1634-42.
doi: 10.1086/588385.

Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects

Mary K Wloch  1 , Larry R Smith, Souphaphone Boutsaboualoy, Luane Reyes, Christina Han, Jackie Kehler, Heather D Smith, Linda Selk, Ryotaro Nakamura, Janice M Brown, Thomas Marbury, Anna Wald, Alain Rolland, David Kaslow, Thomas Evans, Michael Boeckh
Affiliations
Clinical Trial

Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects

Mary K Wloch et al. J Infect Dis. .

Abstract

Background: VCL-CB01, a candidate cytomegalovirus (CMV) DNA vaccine that contains plasmids encoding CMV phosphoprotein 65 (pp65) and glycoprotein B (gB) to induce cellular and humoral immune responses and that is 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 and 22 CMV seropositive) 18-43 years old. Thirty-two subjects received 1- 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 enzyme-linked immunosorbant assay and/or ex vivo interferon (IFN)-gamma enzyme-linked immunospot assay, was documented in 45.5% of CMV-seronegative subjects and in 25.0% of CMV-seropositive subjects who received the full vaccine series, and 68.1% of CMV-seronegative subjects had memory IFN-gamma T cell responses at week 32.

Conclusion: The safety and immunogenicity data from this trial support further evaluation of VCL-CB01.

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Figures

Figure 1
Figure 1. T-cell Responses for CMV-Seronegative Subjects
Ex vivo gamma interferon (IFN-γ) ELISPOT assays were performed as described in Materials and Methods. Individual cytomegalovirus (CMV) phosphoprotein 65 (pp65) T-cell responses are shown for CMV-seronegative subjects vaccinated with 1 mg (A), or 5 mg (B) doses of VCL-CB01 at 0, 2, and 8 weeks and CMV-seronegative subjects vaccinated with 5 mg doses of VCL-CB01 at 0, 3, 7, and 28 days (C).
Figure 2
Figure 2. Antibody Responses for CMV-Seronegative Subjects
Cytomegalovirus (CMV) glycoprotein B (gB) ELISAs were performed as described in Materials and Methods. A serum specimen was positive in the assay if the absorbance for serum at a 1:100 dilution was greater than a reactivity threshold calculated as 2.5 times the absorbance of pooled CMV-seronegative sera at a 1:100 dilution. Anti-gB levels in EU/mL were interpolated from a standard curve using serum with well defined reactivity to CMV gB. In a survey of 76 CMV-seronegative sera and 55 CMV-seropositive sera the assay had a sensitivity of 100% and specificity of 95%. The results for the CMV-seropositive sera ranged from 16,350 EU/mL to 413,440 EU/mL with a median value of 154,560 EU/mL (authors’ unpublished data). Individual gB antibody responses are shown for CMV-seronegative subjects vaccinated with 1 mg (A), or 5 mg (B) doses of VCL-CB01 at 0, 2, and 8 weeks and CMV-seronegative subjects vaccinated with 5 mg doses of VCL-CB01 at 0, 3, 7, and 28 days (C).
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Comment in

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