Muller S, Margolin D H, Min G, Lou D, Nara P, Axthelm M K, Kohler H
Immpheron, Inc., Lexington, KY 40503, USA.
Scand J Immunol. 2001 Oct;54(4):383-95. doi: 10.1046/j.1365-3083.2001.00982.x.
Three macaques infected with SHIV-IIIB and expressing the shared 1F7-idiotypic marker on antibodies against HIV-1 gp120, were injected intravenously with 1F7 monoclonal antibodies (MoAb). As controls, a SHIV-IIIB-infected macaque was injected with a HIV-unrelated mouse monoclonal isotype antibody (TEPC-183) and two healthy, noninfected macaques were injected with MoAb 1F7. 1F7-id-expressing antibodies against gp120-IIIB decreased in two of the three MoAb 1F7-treated macaques and then rebounded. Importantly, antibodies binding to envelope proteins of heterologous HIV-1 strains MN, CM, and SF2, which were low or not detectable before the MoAb 1F7 treatment, increased rapidly following MoAb inoculations in all three 1F7 MoAb treated macaques, but not in the macaque injected with control MoAb TEPC-183. Newly arising antibodies reacting with heterologous virus, i.e. HIV-1 gp120-MN, SF2, and CM did not express 1F7-id. Surprisingly, significant increases of antibodies were also observed in the 1F7-inoculated macaques' antibodies directed to non-HIV antigens (DNP, peptides and BSA). The noninfected control animals did not produce antibodies to these antigens despite MoAb 1F7 treatment. These data show that the MoAb 1F7 injections of chronically SHIV-IIIB-infected macaques resulted in idiotype-specific clonal suppression with broadening the antibody response to HIV envelope proteins.
三只感染了SHIV-IIIB且在针对HIV-1 gp120的抗体上表达共享1F7独特型标记的猕猴,经静脉注射1F7单克隆抗体(MoAb)。作为对照,一只感染SHIV-IIIB的猕猴注射了一种与HIV无关的小鼠单克隆同型抗体(TEPC-183),两只健康未感染的猕猴注射了MoAb 1F7。在三只接受MoAb 1F7治疗的猕猴中,有两只体内针对gp120-IIIB的表达1F7-id的抗体减少,随后又反弹。重要的是,在MoAb 1F7治疗前水平较低或无法检测到的、与异源HIV-1毒株MN、CM和SF2包膜蛋白结合的抗体,在所有三只接受1F7 MoAb治疗的猕猴中,MoAb接种后迅速增加,但在注射对照MoAb TEPC-183的猕猴中未出现这种情况。新产生的与异源病毒反应的抗体,即HIV-1 gp120-MN、SF2和CM,不表达1F7-id。令人惊讶的是,在接种1F7的猕猴中,针对非HIV抗原(DNP、肽和BSA)的抗体也出现了显著增加。尽管接受了MoAb 1F7治疗,未感染的对照动物并未产生针对这些抗原的抗体。这些数据表明,对慢性感染SHIV-IIIB的猕猴注射MoAb 1F7导致独特型特异性克隆抑制,并拓宽了对HIV包膜蛋白的抗体反应。