Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody

Authors:

• Heydarchi, Behnaz
• Fong, Danielle S.
• Gao, Hongmei
• Salazar-Quiroz, Natalia A.
• Edwards, Jack M.
• Gonelli, Christopher A.
• Grimley, Samantha
• Aktepe, Turgut E.
• Mackenzie, Charlene
• Wales, William J.
• van Gils, Marit J.
• Cupo, Albert
• Rouiller, Isabelle
• Gooley, Paul R.
• Moore, John P.
• Sanders, Rogier W.
• Montefiori, David
• Sethi, Ashish
• Purcell, Damian F.J.

Details:

Cell Reports Medicine, Volume 3, Issue 5, 2022-05-17

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Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than a majority of CD4bs bNAbs isolated so far. MEL-1872 mAb with CDRH3 of 57 amino acids shows more potency (geometric mean half-maximal inhibitory concentration [IC50]: 0.009 μg/mL; breadth: 66%) than VRC01 against clade B viruses (29-fold) and than CHO1-31 against tested clade A viruses (21-fold). It also shows more breadth and potency than NC-Cow1, the only other reported anti-HIV-1 bovine bNAb, which has 60% breadth with geometric mean IC50 of 0.090 μg/mL in this study. Using successive different stable-structured SOSIP trimers in bovines can elicit bNAbs focusing on epitopes ubiquitous across subtypes. Furthermore, the cross-clade selection strategy also results in ultra-potent bNAbs.