Journal
CELL REPORTS MEDICINE
Volume 3, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.xcrm.2022.100635
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Funding
- Australian NHRMC-EU Horizons 2020 Grant [APP1115828]
- European AIDS Vaccine Initiative 2020 (EAVI 2020)
- Australian Centre for HIV-1 and Hepatitis Virology Research
- Melbourne HIV-1 Cure Consortium
- University of Melbourne Early Career Research Grant
- National Institutes of Health [APP1115828, P01 AI110657]
- European Union's Horizon 2020 Research and Innovation Programme [HSN272201800004C]
- [681137]
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In this study, HIV-1 vaccination of cows resulted in the production of broadly neutralizing antibodies (bNAbs), and a more potent bNAb was identified. The use of stable SOSIP trimers in cows can induce the production of bNAbs targeting epitopes ubiquitous across subtypes.
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 mu g/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 mg/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.
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