TY - JOUR
T1 - Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth
AU - Chukwuma, Valentine U.
AU - Kose, Nurgun
AU - Noah Sather, D.
AU - Sapparapu, Gopal
AU - King, Hannah
AU - Singh, Vidisha
AU - Lampley, Rebecca
AU - Malherbe, Delphine C.
AU - Ditto, Noah T.
AU - Sullivan, Jonathan T.
AU - Barnes, Trevor
AU - Doranz, Benjamin J.
AU - Labranche, Celia C.
AU - Montefiori, David C.
AU - Kalams, Spyros A.
AU - Haigwood, Nancy L.
AU - Crowe, James E.
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases through U.S. National Institutes of Health grants U01 AI 78407, (J.E.C., S.A.K.), P01 AI 078064 (N.L.H. and J.E.C., S.A.K.), R43 AI096936 (BJD). All other authors declare no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Several authors are employed by Integral Molecular, Inc. This funder provided support in the form of salaries for authors who contributed epitope mapping data including epitope data collection and analysis [JTS, TB, BJD], but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This work was supported by the National Institute of Allergy and Infectious Diseases through U.S. National Institutes of Health grants U01 AI 78407, (J.E.C., S.A.K.), P01 AI 078064 (N.L.H. and J.E.C., S.A.K.), R43 AI096936 (BJD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Several authors are employed by Integral Molecular, Inc. This funder provided support in the form of salaries for authors who contributed epitope mapping data including epitope data collection and analysis [JTS, TB, BJD], but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. All other authors declare no conflict of interest.
Publisher Copyright:
© 2018 Chukwuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0209437
DO - 10.1371/journal.pone.0209437
M3 - Article
C2 - 30566528
AN - SCOPUS:85058846767
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e0209437
ER -