Journal article
Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody
B Heydarchi, DS Fong, H Gao, NA Salazar-Quiroz, JM Edwards, CA Gonelli, S Grimley, TE Aktepe, C Mackenzie, WJ Wales, MJ van Gils, A Cupo, I Rouiller, PR Gooley, JP Moore, RW Sanders, D Montefiori, A Sethi, DFJ Purcell
Cell Reports Medicine | Published : 2022
Abstract
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 repor..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was conducted under animal ethics approval 2015-17 from the Victorian State Government DEDJTR Research and Extension Animal Ethics Committee. Funding support was provided to D.F.J.P. from the Australian NHRMC-EU Horizons 2020 Grant (APP1115828) , as a partner in the European AIDS Vaccine Initiative 2020 (EAVI 2020) , from the Australian Centre for HIV-1 and Hepatitis Virology Research; to B.H. from the Melbourne HIV-1 Cure Consortium and the Australian Centre for HIV-1 and Hepatitis Virology Research; to A.S. from the University of Melbourne Early Career Research Grant; and to J.P.M. from grant P01 AI110657 and to D.M. from grant HSN272201800004C from the National Institutes of Health. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 681137. We acknowledge contributions of Leanne Horstman, Greg Morris, and Lianne Dorling (Department Jobs, Precincts and Resources, Victoria) for veterinarian support and animal husbandry and George Lovrecs and Brian Muller for technical support.