Safety and immunogenicity of Towne cytomegalovirus vaccine with or without adjuvant recombinant interleukin-12.

The Towne, human cytomegalovirus (CMV) vaccine is safe and immunogenic but has not prevented infection at doses tested to date. We administered 3000 pfu Towne CMV vaccine, with or without adjuvant recombinant interleukin-12 (rhIL-12), to CMV-seronegative healthy volunteers and then measured CMV gB-specific IgG titers and CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression after stimulation with whole viral lysate and immunodominant peptide CMV antigens. Adjuvant rhIL-12 at doses up to 2 microg were well-tolerated and associated with (1) dose-related increases in peak anti-CMV gB IgG titers (though not in sustained titers), (2) dose-related increases in the weak CMV viral lysate-specific CD4+ T cell proliferation responses induced by vaccine alone after 360 days of follow-up, and (3) decreases in the very robust CMV IE-specific peak CD4+ T cell and Day 360 CD8+ T cell proliferation responses induced by the vaccine alone. Also, qualitative CD8+ T cell IFNgamma responses to stimulation with the immunodominant CMV antigen, pp65, tended to occur more frequently in vaccinees who received 0.5-2.0 microg rhIL-12 compared to lower dose or no rhIL-12. Thus, adjuvant IL-12 may be a promising strategy for improving antibody and T cell immune responses to a CMV vaccine.

Antigen-specific T cell responses induced by Towne cytomegalovirus (CMV) vaccine in CMV-seronegative vaccine recipients.

BACKGROUND: Towne cytomegalovirus (CMV) vaccine is safe and immunogenic, though its protective efficacy has yet to be optimized. OBJECTIVE: Describe antigen-specific T cell responses to Towne vaccination. STUDY DESIGN: 3000 pfu Towne CMV vaccine were given to 12 CMV-seronegative volunteers. CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression were measured by flow cytometry after stimulation with CMV lysate or peptides. RESULTS: All vaccinees developed CD4+ and CD8+ T cell proliferation and CD4+ T cell IFNgamma responses to multiple CMV antigens, but their CD8+ T cells had low or undetectable IFNgamma responses to pp65 peptide pool. The seven HLA-A2+ subjects had higher CD8+ T cell proliferation and IFNgamma responses to IE than pp65, and two never developed CD8+ T cell IFNgamma responses to pp65. Peak CD4+ T cell IFNgamma responses to CMV lysate were lower than values observed in natural CMV seropositives. Initial CD4+ and CD8+ T cell responses to lysate and pp65 waned after 12 months to levels that were lower than those in healthy CMV seropositives, while vaccinees' CD8+ T cell responses to IE were robust and prolonged. CONCLUSION: Correlating CMV antigen-specific T cell responses with clinical protective efficacy may facilitate future CMV vaccine development.