title: HIV/SIV DNA vaccine combined with protein in a co-immunization protocol elicits highest humoral responses to envelope in mice and macaques.
abstract: Vaccination with HIV/SIV DNAs elicits potent T-cell responses. To improve humoral immune responses, we combined DNA and protein in a co-immunization protocol using in vivo electroporation in mice and macaques. DNA&protein co-immunization induced higher antibody responses than DNA or protein alone, or DNA prime/protein boost in mice. DNA&protein co-immunization induced similar levels of cellular responses as those obtained by DNA only vaccination. The inclusion of SIV or HIV Env gp120 protein did not impair the development of cellular immune responses elicited by DNA present in the vaccine regimen. In macaques, the DNA&protein co-immunization regimen also elicited higher levels of humoral responses with broader cross-neutralizing activity. Despite the improved immunogenicity of DNA&protein co-immunization, the protein formulation with the EM-005 (GLA-SE) adjuvant further increased the anti-Env humoral responses. Dissecting the contribution of EM-005, we found that its administration upregulated the expression of co-stimulatory molecules and stimulated cytokine production, especially IL-6, by dendritic cells in vivo. These terminally differentiated, mature, dendritic cells possibly promote higher levels of humoral responses, supporting the inclusion of the EM-005 adjuvant with the vaccine. Thus, DNA&protein co-immunization is a promising strategy to improve the rapidity of development, magnitude and potency of the humoral immune responses.
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Li
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: Rachel Kelly
authors.initials: RK
authors.lastname: Beach
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D056738:Cross Protection; D003713:Dendritic Cells / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D015850:Interleukin-6 / Q000276:immunology; D008251:Macaca; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015302:Simian Immunodeficiency Virus; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; C069623:gp120 protein, Simian immunodeficiency virus
keywords: Adjuvant; Antibody; Cellular responses; Dendritic cell maturation; Electroporation; Humoral responses; Immunization; Neutralizing antibody; Vaccination