Nature2014-06-18 4:19 PM

关于能中和HIV-1的抗体的形成方式研究 Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies


更好了解能中和HIV-1的抗体是怎样生成的,会有助于设计改进的艾滋病疫苗。现在,John Mascola及同事阐述了一个重要类别的能中和HIV-1的抗体的免疫通道,即那些以病毒包膜的可变V1V2区域为目标的抗体。这些抗体在HIV感染早期阶段比CD4-结合点抗体更经常地被触发,“亲和力成熟”(一个有利于在能增强抗原结合的抗体可变区域发生突变的过程) 程度也不太高。


Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01–12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.






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