title: Bovine alpha-2-HS-glycoprotein functions as a booster antigen for efficiently stimulating humoral immune responses to CCR5 and SIVmac239 envelope glycoprotein.
abstract: The presence of anti-CCR5 and anti-HIV-1 envelope glycoprotein (ENV) gp41 antibodies (Abs) at sites of HIV-1 exposure was effective in preventing its transmission to HIV-1-exposed seronegative (ESN) subjects. Here, we design an immunogen that can induce Abs against CCR5 and SIVmac239 ENV simultaneously and show that bovine alpha-2-HS-glycoprotein (bAHSG) functions as a booster antigen for efficiently stimulating humoral immune responses to CCR5 and ENV. Initially, we generated a rhesus CCR5-derived cyclopeptide (cDDR5) conjugated with a recombinant trimeric SIVmac239 Env. When inguinally administered to rhesus macaques, the immunogen simultaneously induced both anti-CCR5 and anti-ENV Abs in sera, and the purified serum IgG fraction exerted an inhibitory effect on SIVmac239 infection in vitro. When further boosted with bAHSG, the responses of both Abs were significantly enhanced. To examine the cross-reactivity of bAHSG, it was administered to naïve cynomolgus macaques. The results showed a statistically significant increase in IgG response against cynomolgus CCR5 and SIVmac239 ENV, and the induction of neutralizing activity against SIVmac239. These findings suggest that bAHSG is useful for immune strategies aimed at generating Abs against CCR5 and ENV simultaneously to confer HIV-protective immunity.
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Otsubo
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Seizo
authors.initials: S
authors.lastname: Yashiro
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Kiyoteru
authors.initials: K
authors.lastname: Nozaki
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Kiyonaga
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Ryotarou
authors.initials: R
authors.lastname: Mitsumata
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Masuyama
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Muneoka
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Nobutoki
authors.initials: N
authors.lastname: Takamune
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Electronic address: misumi@gpo.kumamoto-u.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D002417:Cattle; D015686:Gene Products, env / Q000276:immunology*; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D056724:Immunity, Humoral; D007117:Immunization, Secondary / Q000379:methods*; D008252:Macaca fascicularis; D019713:Receptors, CCR5 / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D060749:alpha-2-HS-Glycoprotein / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000941:Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D060749:alpha-2-HS-Glycoprotein
keywords: Alpha-2-HS-glycoprotein; CCR5; Cross-reacting antigen; HIV; HIV-1 vaccine; SIV; SIVmac239 ENV; human immunodeficiency virus; simian immunodeficiency virus