PDF(Pubmed)
Abstract：
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.
摘要：
靶向甲型流感病毒(IAV)的血凝素(HA)茎的广义中和抗体(bnAb)倾向于有效对抗第1组或第2组病毒多样性。在罕见的情况下，群间保护性bnAb可以通过人抗体互补体产生,其适应组1和组2茎之间保守的聚糖差异。我们应用种系参与纳米颗粒免疫原，从人源化小鼠模型中的生理前体频率中引发一类交叉组bnAb。交叉组保护取决于B细胞库内人bnAb前体的存在，以及在CDRH2环中富集N55T取代的疫苗扩增抗体，bnAb类的标志。在结构上,这种单突变引入了一个灵活的支点来适应糖基化差异,并且可以单独实现交叉基团保护.因此，广泛的IAV免疫可以通过最小的抗原输入和异常简单的抗体开发途径从种系库扩展。
