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

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

doi:https://doi.org/10.1016/j.xcrm.2022.100635

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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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 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.

Original language	English
Article number	100635
Journal	Cell Reports Medicine
Volume	3
Issue number	5
DOIs	https://doi.org/10.1016/j.xcrm.2022.100635
Publication status	Published - 17 May 2022

Keywords

CDRH3
HIV-1
antibody
antiretroviral
cows
envelope glycoprotein
neutralization
vaccine

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https://doi.org/10.1016/j.xcrm.2022.100635

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Heydarchi, B., Fong, D. S., Gao, H., Salazar-Quiroz, N. A., Edwards, J. M., Gonelli, C. A., Grimley, S., Aktepe, T. E., Mackenzie, C., Wales, W. J., van Gils, M. J., Cupo, A., Rouiller, I., Gooley, P. R., Moore, J. P., Sanders, R. W., Montefiori, D., Sethi, A., & Purcell, D. F. J. (2022). Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody. Cell Reports Medicine, 3(5), Article 100635. https://doi.org/10.1016/j.xcrm.2022.100635

@article{ebce599349b44941ac41fd99e2b556f7,

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

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 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.",

keywords = "CDRH3, HIV-1, antibody, antiretroviral, cows, envelope glycoprotein, neutralization, vaccine",

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

note = "Funding Information: 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{\textquoteright}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. Funding Information: 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. Conceptualization and oversight of the experiment, B.H. and D.F.J.P.; antigen B cell sorting, B.H.; PCR and antibody cloning, B.H. and J.M.E.; antibody gene analysis, B.H. and N.A.S.-Q.; antibody expression and purification, B.H. J.M.E. and S.G.; antibody characterization, neutralization, and mutagenesis experiments, B.H. D.S.F. N.A.S.-Q. H.G. and D.M.; provided proteins for immunization, R.W.S. M.J.v.G. J.P.M. A.C. and C.A.G.; structural work and analysis, A.S.; polyreactivity assays, B.H. and T.E.A.; cow immunization, D.F.J.P. W.J.W. and C.M.; analysis, figures, and original draft of manuscript, B.H. D.S.F. A.S. and N.A.S.-Q.; review and editing of the manuscript, B.H. D.S.F. H.G. N.A.S.-Q. J.M.E. C.A.G. S.G. T.E.A. C.M. W.J.W. M.J.v.G. A.C. I.R. P.R.G. J.P.M. R.W.S. D.M. A.S. and D.F.J.P.; funding acquisition, D.F.J.P. B.H. and A.S. B.H. and D.F.J.P. are inventors on a corresponding patent from University of Melbourne: HIV-1 antibodies PCT/AU2021/050593. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = may,

day = "17",

doi = "https://doi.org/10.1016/j.xcrm.2022.100635",

language = "English",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "5",

}

Heydarchi, B, Fong, DS, Gao, H, Salazar-Quiroz, NA, Edwards, JM, Gonelli, CA, Grimley, S, Aktepe, TE, Mackenzie, C, Wales, WJ, van Gils, MJ, Cupo, A, Rouiller, I, Gooley, PR, Moore, JP, Sanders, RW, Montefiori, D, Sethi, A & Purcell, DFJ 2022, 'Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody', Cell Reports Medicine, vol. 3, no. 5, 100635. https://doi.org/10.1016/j.xcrm.2022.100635

TY - JOUR

T1 - Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody

AU - Heydarchi, Behnaz

AU - Fong, Danielle S.

AU - Gao, Hongmei

AU - Salazar-Quiroz, Natalia A.

AU - Edwards, Jack M.

AU - Gonelli, Christopher A.

AU - Grimley, Samantha

AU - Aktepe, Turgut E.

AU - Mackenzie, Charlene

AU - Wales, William J.

AU - van Gils, Marit J.

AU - Cupo, Albert

AU - Rouiller, Isabelle

AU - Gooley, Paul R.

AU - Moore, John P.

AU - Sanders, Rogier W.

AU - Montefiori, David

AU - Sethi, Ashish

AU - Purcell, Damian F. J.

N1 - Funding Information: 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. Funding Information: 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. Conceptualization and oversight of the experiment, B.H. and D.F.J.P.; antigen B cell sorting, B.H.; PCR and antibody cloning, B.H. and J.M.E.; antibody gene analysis, B.H. and N.A.S.-Q.; antibody expression and purification, B.H. J.M.E. and S.G.; antibody characterization, neutralization, and mutagenesis experiments, B.H. D.S.F. N.A.S.-Q. H.G. and D.M.; provided proteins for immunization, R.W.S. M.J.v.G. J.P.M. A.C. and C.A.G.; structural work and analysis, A.S.; polyreactivity assays, B.H. and T.E.A.; cow immunization, D.F.J.P. W.J.W. and C.M.; analysis, figures, and original draft of manuscript, B.H. D.S.F. A.S. and N.A.S.-Q.; review and editing of the manuscript, B.H. D.S.F. H.G. N.A.S.-Q. J.M.E. C.A.G. S.G. T.E.A. C.M. W.J.W. M.J.v.G. A.C. I.R. P.R.G. J.P.M. R.W.S. D.M. A.S. and D.F.J.P.; funding acquisition, D.F.J.P. B.H. and A.S. B.H. and D.F.J.P. are inventors on a corresponding patent from University of Melbourne: HIV-1 antibodies PCT/AU2021/050593. The other authors declare no competing interests. Publisher Copyright: © 2022 The Author(s)

PY - 2022/5/17

Y1 - 2022/5/17

N2 - 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.

AB - 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.

KW - CDRH3

KW - HIV-1

KW - antibody

KW - antiretroviral

KW - cows

KW - envelope glycoprotein

KW - neutralization

KW - vaccine

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U2 - https://doi.org/10.1016/j.xcrm.2022.100635

DO - https://doi.org/10.1016/j.xcrm.2022.100635

M3 - Article

C2 - 35584627

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 5

M1 - 100635

ER -

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

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Keywords

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