title: Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates.
abstract: Epidemiological and experimental data suggest that both robust neutralizing antibodies and potent cellular responses play important roles in controlling primary HIV-1 infection. In this study we have investigated the induction of systemic and mucosal immune responses to HIV gp120 monomer immunogen administered intranasally in a novel, oil-in-water nanoemulsion (NE) adjuvant. Mice and guinea pigs intranasally immunized by the application of recombinant HIV gp120 antigen mixed in NE demonstrated robust serum anti-gp120 IgG, as well as bronchial, vaginal, and serum anti-gp120 IgA in mice. The serum of these animals demonstrated antibodies that cross-reacted with heterologous serotypes of gp120 and had significant neutralizing activity against two clade-B laboratory strains of HIV (HIVBaL and HIVSF162) and five primary HIV-1 isolates. The analysis of gp120-specific CTL proliferation, INF-gamma induction, and prevalence of anti-gp120 IgG2 subclass antibodies indicated that nasal vaccination in NE also induced systemic, Th1-polarized cellular immune responses. This study suggests that NE should be evaluated as a mucosal adjuvant for multivalent HIV vaccines.
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Anna U
authors.initials: AU
authors.lastname: Bielinska
authors.forename: Katarzyna W
authors.initials: KW
authors.lastname: Janczak
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Landers
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D049109:Cell Proliferation; D003429:Cross Reactions; D004655:Emulsions / Q000008:administration & dosage*; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000737:chemistry / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004655:Emulsions; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; C514793:gp120 protein, Human immunodeficiency virus 1; D007371:Interferon-gamma