Bielinska Anna U, Janczak Katarzyna W, Landers Jeffrey J, Markovitz David M, Montefiori David C, Baker James R
Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), University of Michigan, Ann Arbor, Michigan 48109, USA.
AIDS Res Hum Retroviruses. 2008 Feb;24(2):271-81. doi: 10.1089/aid.2007.0148.
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.
流行病学和实验数据表明,强大的中和抗体和有效的细胞反应在控制原发性HIV-1感染中都起着重要作用。在本研究中,我们调查了在一种新型水包油纳米乳剂(NE)佐剂中鼻内给予HIV gp120单体免疫原后全身和黏膜免疫反应的诱导情况。通过应用混合在NE中的重组HIV gp120抗原进行鼻内免疫的小鼠和豚鼠,表现出强大的血清抗gp120 IgG,以及小鼠支气管、阴道和血清中的抗gp120 IgA。这些动物的血清显示出与gp120异源血清型交叉反应的抗体,并对两种B亚型HIV实验室毒株(HIVBaL和HIVSF162)以及五种原发性HIV-1分离株具有显著的中和活性。对gp120特异性CTL增殖、INF-γ诱导以及抗gp120 IgG2亚类抗体的流行情况分析表明,在NE中进行鼻内疫苗接种也可诱导全身、Th1极化的细胞免疫反应。本研究表明,NE应作为多价HIV疫苗的黏膜佐剂进行评估。