Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California, USA.
Curr Opin HIV AIDS. 2009 Sep;4(5):364-72. doi: 10.1097/COH.0b013e32832e06fe.
Effective vaccine-elicited immunity against HIV-1 infection will likely require broadly neutralizing antibodies to interrupt the fusion-promoting functions of the viral envelope glycoprotein spikes. Efforts in this area have, however, been fraught with challenges. The handful of existing broadly neutralizing monoclonal antibodies has provided information on some of the virus' sites of vulnerability, fueling a decade of structure-informed vaccine design. The fact that very few bnmAbs have been recovered to date illustrates the poor immunogenicity of these epitopes. Recognizing that progress may require more basic information, there has been a notable shift in the field toward identifying new chinks in HIV-1's armor. These efforts are based on the observation that some infected patients develop exceptionally broad serum neutralizing antibodies responses, a better understanding of which would be valuable for vaccine efforts aimed at eliciting similar specificities.
New mapping methodologies are now providing an appreciation of the incidence of specificities similar to the existing known bnmAbs as well as some intriguing insights into novel specificities.
The new information emerging from mapping efforts should help to sharpen efforts to isolate new bnmAbs and moreover, may provide crucial information for the rational design of novel vaccine candidates.
综述目的:有效预防 HIV-1 感染的疫苗可能需要广泛中和抗体来阻断病毒包膜糖蛋白刺突促进融合的功能。然而,在这一领域的努力充满了挑战。少数现有的广泛中和单克隆抗体为了解病毒的一些脆弱部位提供了信息,推动了十年的基于结构的疫苗设计。到目前为止,只有少数 bnmAbs 被发现,这说明了这些表位的免疫原性较差。鉴于进展可能需要更多的基础信息,该领域已经明显转向识别 HIV-1 盔甲上的新弱点。这些努力基于这样的观察,即一些感染患者会产生异常广泛的血清中和抗体反应,如果更好地了解这些反应,将有助于针对引发类似特异性的疫苗努力。
最近的发现:新的绘图方法现在提供了对类似于现有已知 bnmAbs 的特异性的发生率的认识,以及对新特异性的一些有趣的见解。
总结:从绘图工作中出现的新信息应该有助于加强分离新的 bnmAbs 的努力,而且,可能为新型疫苗候选物的合理设计提供关键信息。