Goepfert Paul A, Tomaras Georgia D, Horton Helen, Montefiori David, Ferrari Guido, Deers Mark, Voss Gerald, Koutsoukos Marguerite, Pedneault Louise, Vandepapeliere Pierre, McElrath M Juliana, Spearman Paul, Fuchs Jonathan D, Koblin Beryl A, Blattner William A, Frey Sharon, Baden Lindsey R, Harro Clayton, Evans Thomas
University of Alabama at Birmingham, 908 20th Street South, CCB 328, Birmingham, AL 35294, USA.
Vaccine. 2007 Jan 5;25(3):510-8. doi: 10.1016/j.vaccine.2006.07.050. Epub 2006 Aug 10.
Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system.
Eighty-four HIV uninfected human participants were vaccinated intramuscularly at 0, 1, and 3 months and evaluated for safety. Immune responses were analyzed for the presence of vaccine-induced antibody and T lymphocyte responses.
The vaccines were safe and well tolerated at all doses. Nef-, Tat-, and gp120-specific binding antibodies were induced in all individuals that received the respective antigen, lasting up to 9 months after the final immunization. Antibodies able to neutralize the T-cell laboratory-adapted strain of HIV-1(W61D) were detected in the majority of vacinees, but did not neutralize primary isolates. Envelope-specific antibody-dependent cell cytoxicity was detected in most of the individuals receiving gp120. Robust and persistent HIV-specific lymphoproliferative responses were detected against all subunit proteins in the majority of immunized participants. As expected, HIV-specific CD8 T-cell responses were not detected.
Despite the lack of primary isolate neutralizing antibody induction, the observed high frequency and magnitude of other immune responses warrant further work with this vaccine or vaccine components.
先前研究表明，在恒河猴猴免疫缺陷病毒（SHIV）动物模型系统中，使用与AS02A佐剂系统配制的重组蛋白NefTat和gp120（W61D）可预防艾滋病。
84名未感染HIV的人类参与者在第0、1和3个月进行肌肉注射疫苗，并评估安全性。分析免疫反应，检测疫苗诱导的抗体和T淋巴细胞反应。
所有剂量的疫苗均安全且耐受性良好。在所有接受相应抗原的个体中均诱导出了针对Nef、Tat和gp120的特异性结合抗体，在最后一次免疫后可持续长达9个月。大多数接种疫苗者体内检测到了能够中和HIV-1（W61D）实验室适应株T细胞的抗体，但不能中和原始分离株。在大多数接受gp120的个体中检测到了包膜特异性抗体依赖性细胞毒性。在大多数免疫参与者中，针对所有亚单位蛋白均检测到了强烈且持续的HIV特异性淋巴细胞增殖反应。正如预期的那样，未检测到HIV特异性CD8 T细胞反应。
尽管未诱导出针对原始分离株的中和抗体，但观察到的其他免疫反应的高频率和高强度值得对该疫苗或疫苗成分开展进一步研究。
