{Reference Type}: Journal Article
{Title}: Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
{Author}: Ray R;Nait Mohamed FA;Maurer DP;Huang J;Alpay BA;Ronsard L;Xie Z;Han J;Fernandez-Quintero M;Phan QA;Ursin RL;Vu M;Kirsch KH;Prum T;Rosado VC;Bracamonte-Moreno T;Okonkwo V;Bals J;McCarthy C;Nair U;Kanekiyo M;Ward AB;Schmidt AG;Batista FD;Lingwood D;
{Journal}: Immunity
{Volume}: 57
{Issue}: 5
{Year}: 2024 May 14
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2024.03.022
{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.