Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth

Valentine U. Chukwuma, Nurgun Kose, D. Noah Sather, Gopal Sapparapu, Hannah King, Vidisha Singh, Rebecca Lampley, Delphine Malherbe, Noah T. Ditto, Jonathan T. Sullivan, Trevor Barnes, Benjamin J. Doranz, Celia C. Labranche, David C. Montefiori, Spyros A. Kalams, Nancy Haigwood, James E. Crowe

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Broadly neutralizing antibodies (bNAbs) are rarely elicited by current human immunodeficiency virus type 1 (HIV-1) vaccine designs, but the presence of bNAbs in naturally infected individuals may be associated with high plasma viral loads, suggesting that the magnitude, duration, and diversity of viral exposure may contribute to the development of bNAbs. Here, we report the isolation and characterization of a panel of human monoclonal antibodies (mAbs) from two subjects who developed broadly neutralizing autologous antibody responses during HIV-1 infection. In both subjects, we identified collections of mAbs that exhibited specificity only to a few autologous envelopes (Envs), with some mAbs exhibiting specificity only to a subset of Envs within the quasispecies of a particular sample at one time point. Neutralizing antibodies (NAbs) isolated from these subjects mapped mostly to epitopes in the Env V3 loop region and the CD4 binding site. None of the individual neutralizing mAbs recovered exhibited the cumulative breadth of neutralization present in the serum of the subjects. Surprisingly, however, the activity of polyclonal mixtures comprising individual mAbs that each possessed limited neutralizing activity, could achieve increased breadth of neutralizing activity against autologous isolates. While a single broadly neutralizing antibody targeting one epitope can mediate neutralization breadth, the findings presented here suggest that a cooperative polyclonal process mediated by diverse antibodies with more limited breadth targeting multiple epitopes also can achieve neutralization breadth against HIV-1.

    Original languageEnglish (US)
    Article numbere0209437
    JournalPLoS One
    Volume13
    Issue number12
    DOIs
    StatePublished - Dec 1 2018

    Fingerprint

    Human immunodeficiency virus 1
    Neutralizing Antibodies
    Viruses
    neutralizing antibodies
    neutralization
    HIV-1
    Clone Cells
    Monoclonal Antibodies
    monoclonal antibodies
    clones
    antibodies
    Antibodies
    Epitopes
    epitopes
    Antibody Specificity
    viral load
    Vaccines
    cooperatives
    Virus Diseases
    Binding Sites

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    Chukwuma, V. U., Kose, N., Noah Sather, D., Sapparapu, G., King, H., Singh, V., ... Crowe, J. E. (2018). Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth. PLoS One, 13(12), [e0209437]. https://doi.org/10.1371/journal.pone.0209437

    Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth. / Chukwuma, Valentine U.; Kose, Nurgun; Noah Sather, D.; Sapparapu, Gopal; King, Hannah; Singh, Vidisha; Lampley, Rebecca; Malherbe, Delphine; Ditto, Noah T.; Sullivan, Jonathan T.; Barnes, Trevor; Doranz, Benjamin J.; Labranche, Celia C.; Montefiori, David C.; Kalams, Spyros A.; Haigwood, Nancy; Crowe, James E.

    In: PLoS One, Vol. 13, No. 12, e0209437, 01.12.2018.

    Research output: Contribution to journalArticle

    Chukwuma, VU, Kose, N, Noah Sather, D, Sapparapu, G, King, H, Singh, V, Lampley, R, Malherbe, D, Ditto, NT, Sullivan, JT, Barnes, T, Doranz, BJ, Labranche, CC, Montefiori, DC, Kalams, SA, Haigwood, N & Crowe, JE 2018, 'Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth', PLoS One, vol. 13, no. 12, e0209437. https://doi.org/10.1371/journal.pone.0209437
    Chukwuma, Valentine U. ; Kose, Nurgun ; Noah Sather, D. ; Sapparapu, Gopal ; King, Hannah ; Singh, Vidisha ; Lampley, Rebecca ; Malherbe, Delphine ; Ditto, Noah T. ; Sullivan, Jonathan T. ; Barnes, Trevor ; Doranz, Benjamin J. ; Labranche, Celia C. ; Montefiori, David C. ; Kalams, Spyros A. ; Haigwood, Nancy ; Crowe, James E. / Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth. In: PLoS One. 2018 ; Vol. 13, No. 12.
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