Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates
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作者:
Bielinska, Anna U.
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Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Bielinska, Anna U.
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Janczak, Katarzyna W.
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Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Janczak, Katarzyna W.
[1
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Landers, Jeffrey J.
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Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Landers, Jeffrey J.
[1
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Markovitz, David M.
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Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Markovitz, David M.
[1
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Montefiori, David C.
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Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27706 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Montefiori, David C.
[2
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Baker, James R., Jr.
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Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USAUniv Michigan, MNIMBS, Ann Arbor, MI 48109 USA
Baker, James R., Jr.
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机构:
[1] Univ Michigan, MNIMBS, Ann Arbor, MI 48109 USA
[2] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27706 USA
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.