title: Evaluation of the immune response and protective effects of rhesus macaques vaccinated with biodegradable nanoparticles carrying gp120 of human immunodeficiency virus.
abstract: We previously reported that biodegradable amphiphilic poly(gamma-glutamic acid) nanoparticles (NPs) carrying the recombinant gp120 env protein of the human immunodeficiency virus type 1 (HIV-1) were efficiently taken up by dendritic cells, and induced strong CD8(+) T cell responses against the gp120 in mice. To evaluate gp120-carrying NPs (gp120-NPs) as a vaccine candidate for HIV-1 infection, we vaccinated rhesus macaques with these gp120-NPs and examined the immune response and protective efficacy against a challenge inoculation of simian and human immunodeficiency chimeric virus (SHIV). We found that gp120-NP vaccination induced stronger responses for both gp120-specific cellular and humoral immunity than gp120-alone vaccination. After the challenge inoculation with SHIV, however, the peak value of viral RNA in the peripheral blood was higher in the vaccinated groups, especially the gp120-NP vaccinated group, than naive control group. Higher value of viral load was also maintained in gp120-NP vaccinated group. Furthermore, CD4(+) T cells from the peripheral blood decreased more in the vaccinated groups than the control group. Thus, induced immune responses against gp120 enclosed in NPs were not effective for protection but, conversely enhanced the infection, although the gp120-NPs showed a stronger induction of immune responses against the vaccinated antigen in rhesus macaques. These results support the importance of determining immune correlate of protective immunity for vaccine development against HIV-1 infection.
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Himeno
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ibuki
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Mariko
authors.initials: M
authors.lastname: Horiike
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008253:Macaca mulatta / Q000276:immunology; D053758:Nanoparticles; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral