Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain. This recognition provided an “anchor” for the Abs as the core protein epitope varies, prevented complete neutralization escape, and eventually led to broadening of the response. These findings illustrate how glycan-specific maturation enables a human Ab to cope with pathogen escape mechanisms and will aid in optimization of immunization strategies to induce V2 apex bnAb responses.

Apex广泛中和HIV抗体（bnAbs）识别聚糖和接近包膜（Env）三聚体3倍轴的蛋白质表面，并且是所描述的最有效和最广泛的Abs。已详细研究了来自一个供体的先端bnAb的进化（CAP256），并描述了处于不同成熟阶段的许多Abs。使用多种工程工具，我们调查了聚糖识别在CAP256.VRC26 Ab谱系开发中的参与。我们发现带有唾液酸的聚糖被Ab重链上种系编码和体细胞突变的残基识别。由于核心蛋白表位的变化，这种认识为Abs提供了“锚定”，阻止了中和反应的完全逃逸，并最终导致了反应范围的扩大。