Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
AbCellera Biologics Inc., Vancouver, BC, Canada.
Sci Rep. 2021 Feb 25;11(1):4637. doi: 10.1038/s41598-021-84116-w.
The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.
寡甘露糖特异性广泛中和抗体（bnAbs）的出现促使人们努力开发能够诱导产生类似抗体的免疫原。在这里，我们报告了先前报道的寡甘露糖模拟物的 CRM 缀合物的抗原性和免疫原性。对 HIV 包膜蛋白序列的依赖性较低的寡甘露糖特异性 bnAbs 与糖缀合物表现出强烈的结合，亲和力接近其同源表位的报道值。糖缀合物也被推断为寡甘露糖特异性 bnAbs 的种系前体所识别，尽管亲和力较低，但支持其作为免疫原的潜力。对人抗体转基因小鼠的免疫接种表明，只有 TLR4 刺激佐剂配方才能产生能够结合一系列重组 HIV 三聚体的抗体。这些抗体的结合水平相对较低，这可能解释了它们不能中和 HIV 感染性的原因。尽管如此，这些发现进一步加深了我们对诱导产生 HIV 交叉反应性寡甘露糖特异性抗体的条件的理解，并为改进所诱导的反应提供了下一步的信息。
