Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates

被引:66
作者
Bielinska, Anna U. [1 ]
Janczak, Katarzyna W. [1 ]
Landers, Jeffrey J. [1 ]
Markovitz, David M. [1 ]
Montefiori, David C. [2 ]
Baker, James R., Jr. [1 ]
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
基金
英国惠康基金;
关键词
D O I
10.1089/aid.2007.0148
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:271 / 281
页数:11
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