Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention

doi:10.15698/mic2024.07.826

. 2024 Jul 3:11:207-220.

doi: 10.15698/mic2024.07.826. eCollection 2024.

Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention

Juan C Becerra¹, Lauren Hitchcock¹, Khoa Vu¹, Johannes S Gach¹

Affiliations

PMID: 38975023
PMCID: PMC11224682
DOI: 10.15698/mic2024.07.826

Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention

Juan C Becerra et al. Microb Cell. 2024.

. 2024 Jul 3:11:207-220.

doi: 10.15698/mic2024.07.826. eCollection 2024.

Authors

Juan C Becerra¹, Lauren Hitchcock¹, Khoa Vu¹, Johannes S Gach¹

Affiliation

¹ Department of Medicine, Division of Infectious Diseases, University of California CA, Irvine, Irvine, 92697 USA.

PMID: 38975023
PMCID: PMC11224682
DOI: 10.15698/mic2024.07.826

Abstract

Broadly neutralizing antibodies (bnAbs) targeting the human immunodeficiency virus-1 (HIV-1) have played a crucial role in elucidating and characterizing neutralization-sensitive sites on the HIV-1 envelope spike and in informing vaccine development. Continual advancements in identifying more potent bnAbs, along with their capacity to trigger antibody-mediated effector functions, coupled with modifications to extend their half-life, position them as promising candidates for both HIV-1 treatment and prevention. While current pharmacological interventions have made significant progress in managing HIV-1 infection and enhancing quality of life, no definitive cure or vaccines have been developed thus far. Standard treatments involve daily oral anti-retroviral therapy, which, despite its efficacy, can lead to notable long-term side effects. Recent clinical trial data have demonstrated encouraging therapeutic and preventive potential for bnAb therapies in both HIV-1-infected individuals and those without the infection. This review provides an overview of the advancements in HIV-1-specific bnAbs and discusses the insights gathered from recent clinical trials regarding their application in treating and preventing HIV-1 infection.

Keywords: HIV1; bnAbs; prevention; treatment; viral reservoir.

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Conflict of interest statement

The authors declare that no competing interest exists.

Figures

Figure 1. Examples of potential forms of HIV-1 envelope on the viral surface.(A) Intact envelope spikes consist of three non-covalently bound gp120/gp41 heterodimers embedded in the viral membrane via a transmembrane domain and a cytoplasmic tail. (B) Free monomeric gp120, released through envelope shedding. (C) Shaved gp41 stumps on the viral surface.

Figure 2. Sites of vulnerability on an HIV-1 envelope spike. BnAbs can be directed against several epitopes on gp120 including the CD4bs, the V1/V2 apex, the V3 glycan supersite site, and the silent face as well as epitopes on gp41 such as the gp41-gp120 interface region, the fusion peptide and the MPER. Examples of bnAbs targeting these sites are shown in Table 1.

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[1] Binley J M, Wrin T, Korber B, Zwick M B, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos C J, Burton D R. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol. 2004;78(23):13232–13252. doi: 10.1128/JVI.78.23.13232-13252.2004. - DOI - PMC - PubMed

[2] Binley J M, Wrin T, Korber B, Zwick M B, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos C J, Burton D R. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol. 2004;78(23):13232–13252. doi: 10.1128/JVI.78.23.13232-13252.2004. - DOI - PMC - PubMed

[3] Huang J, Kang B H, Pancera M, Lee J H, Tong T, Feng Y, Imamichi H, Georgiev I S, Chuang G Y, Druz A, Doria-Rose N A, Laub L, Sliepen K, Gils M J Van, Peña A T De La, Derking R, Klasse P J, Migueles S A, Bailer R T, Alam M, Pugach P, Haynes B F, Wyatt R T, Sanders R W, Binley J M, Ward A B, Mascola J R, Kwong P D, Connors M. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014;515(7525):138–142. doi: 10.1038/nature13601. - DOI - PMC - PubMed

[4] Huang J, Kang B H, Pancera M, Lee J H, Tong T, Feng Y, Imamichi H, Georgiev I S, Chuang G Y, Druz A, Doria-Rose N A, Laub L, Sliepen K, Gils M J Van, Peña A T De La, Derking R, Klasse P J, Migueles S A, Bailer R T, Alam M, Pugach P, Haynes B F, Wyatt R T, Sanders R W, Binley J M, Ward A B, Mascola J R, Kwong P D, Connors M. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014;515(7525):138–142. doi: 10.1038/nature13601. - DOI - PMC - PubMed

[5] Scharf L, Wang H, Gao H, Chen S, Mcdowall A W, Bjorkman P J. Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. Cell. 2015;162(6):1379–1390. doi: 10.1016/j.cell.2015.08.035. - DOI - PMC - PubMed

[6] Scharf L, Wang H, Gao H, Chen S, Mcdowall A W, Bjorkman P J. Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. Cell. 2015;162(6):1379–1390. doi: 10.1016/j.cell.2015.08.035. - DOI - PMC - PubMed

[7] Williams L D, Ofek G, Schätzle S, Mcdaniel J R, Lu X, Nicely N I, Wu L, Lougheed C S, Bradley T, Louder M K, Mckee K, Bailer R T, Dell S O', Georgiev I S, Seaman M S, Parks R J, Marshall D J, Anasti K, Yang G, Nie X, Tumba N L, Wiehe K, Wagh K, Korber B, Kepler T B, Alam S Munir, Morris L, Kamanga G, Cohen M S, Bonsignori M, et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Sci Immunol. 2017;2(7):2200–2200. doi: 10.1126/sciimmunol.aal2200. - DOI - PMC - PubMed

[8] Williams L D, Ofek G, Schätzle S, Mcdaniel J R, Lu X, Nicely N I, Wu L, Lougheed C S, Bradley T, Louder M K, Mckee K, Bailer R T, Dell S O', Georgiev I S, Seaman M S, Parks R J, Marshall D J, Anasti K, Yang G, Nie X, Tumba N L, Wiehe K, Wagh K, Korber B, Kepler T B, Alam S Munir, Morris L, Kamanga G, Cohen M S, Bonsignori M, et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Sci Immunol. 2017;2(7):2200–2200. doi: 10.1126/sciimmunol.aal2200. - DOI - PMC - PubMed

[9] Walker L M, Huber M, Doores K J, Falkowska E, Pejchal R, Julien J P, Wang S K, Ramos A, Chan-Hui P Y, Moyle M, Mitcham J L, Hammond P W, Olsen O A, Phung P, Fling S, Wong C H, Phogat S, Wrin T, Simek M D, Koff W C, Wilson I A, Burton D R, Poignard P, Investigators PGP. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477(7365):466–470. doi: 10.1038/nature10373. - DOI - PMC - PubMed

[10] Walker L M, Huber M, Doores K J, Falkowska E, Pejchal R, Julien J P, Wang S K, Ramos A, Chan-Hui P Y, Moyle M, Mitcham J L, Hammond P W, Olsen O A, Phung P, Fling S, Wong C H, Phogat S, Wrin T, Simek M D, Koff W C, Wilson I A, Burton D R, Poignard P, Investigators PGP. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477(7365):466–470. doi: 10.1038/nature10373. - DOI - PMC - PubMed

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Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention

Affiliation

Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention

Authors

Affiliation

Abstract

Conflict of interest statement

Figures

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References

LinkOut - more resources

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