title: Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus.
abstract: The combination of multiple HIV antigens in a vaccine can broaden antiviral immune responses. In this study, we used NDV vaccine strain LaSota to generate rNDV (rLaSota/optGag) expressing human codon optimized p55 Gag protein of HIV-1. We examined the effect of co-immunization of rLaSota/optGag with rNDVs expressing different forms of Env protein gp160, gp120, gp140L [a version of gp140 that lacked cytoplasmic tail and contained complete membrane-proximal external region (MPER)] and gp140S (a version of gp140 that lacked cytoplasmic tail and distal half of MPER) on magnitude and breadth of humoral, mucosal and cellular immune responses in guinea pigs and mice. Our results showed that inclusion of rLaSota/optGag with rNDVs expressing different forms of Env HIV Gag did not affect the Env-specific humoral and mucosal immune responses in guinea pigs and that the potent immune responses generated against Env persisted for at least 13 weeks post immunization. The highest Env-specific humoral and mucosal immune responses were observed with gp140S+optGag group. The neutralizing antibody responses against HIV strains BaL.26 and MN.3 induced by gp140S+optGag and gp160+optGag were higher than those elicited by other groups. Inclusion of Gag with gp160, gp140S and gp140L enhanced the level of Env-specific IFN-γ-producing CD8(+) T cells in mice. Inclusion of Gag with gp160 and gp140L also resulted in increased Env-specific CD4(+) T cells. The level of Gag-specific CD8(+) and CD4(+) T cells was also enhanced in mice immunized with Gag along with gp140S and gp120. These results indicate lack of antigen interference in a vaccine containing rNDVs expressing Env and Gag proteins.
authors.affiliation: a Virginia-Maryland Regional College of Veterinary Medicine ; University of Maryland ; College Park , MD USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Khattar
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Palaniyandi
authors.forename: Sweety
authors.initials: S
authors.lastname: Samal
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D015686:Gene Products, env / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009522:Newcastle disease virus / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D004337:Drug Carriers; D015686:Gene Products, env; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma
keywords: HIV-1 Env; HIV-1 Gag; Newcastle disease virus; guinea pigs; immune responses; mice