Bailey B Banach, Sergei Pletnev, Adam S Olia, Kai Xu, Baoshan Zhang, Reda Rawi, Tatsiana Bylund, Nicole A Doria-Rose, Thuy Duong Nguyen, Ahmed S Fahad, Myungjin Lee, Bob C Lin, Tracy Liu, Mark K Louder, Bharat Madan, Krisha McKee, Sijy O'Dell, Mallika Sastry, Arne Schön, Natalie Bui, Chen-Hsiang Shen, Jacy R Wolfe, Gwo-Yu Chuang, John R Mascola, Peter D Kwong, Brandon J DeKosky
The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel...
November 21, 2023: Nature Communications