title: Safety and immunogenicity of Towne cytomegalovirus vaccine with or without adjuvant recombinant interleukin-12.
abstract: 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.
authors.affiliation: Positive Health Program, Department of Medicine, University of California San Francisco, and San Francisco General Hospital General Clinical Research Center, CA 94110, United States. mjacobson@php.ucsf.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jacobson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Barry
authors.initials: B
authors.lastname: Bredt
authors.forename: Laurie
authors.initials: L
authors.lastname: Agrillo
authors.forename: Douglas
authors.initials: D
authors.lastname: Black
authors.forename: C Lorrie
authors.initials: CL
authors.lastname: Epling
authors.forename: Alexander
authors.initials: A
authors.lastname: Carvidi
authors.forename: Terence
authors.initials: T
authors.lastname: Ho
authors.forename: Raji
authors.initials: R
authors.lastname: Bains
authors.forename: Valerie
authors.initials: V
authors.lastname: Girling
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Adler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12