Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding.

Longo NS, Sutton MS, Shiakolas AR, Guenaga J, Jarosinski MC, Georgiev IS, McKee K, Bailer RT, Louder MK, O'Dell S, Connors M, Wyatt RT, Mascola JR, Doria-Rose NA
J Virol. 2016 90 (23): 10574-10586

PMID: 27654288 · PMCID: PMC5110179 · DOI:10.1128/JVI.01012-16

One of the goals of HIV-1 vaccine development is the elicitation of neutralizing antibodies against vulnerable regions on the envelope glycoprotein (Env) viral spike. Broadly neutralizing antibodies targeting the Env glycan-V3 region (also called the N332 glycan supersite) have been described previously, with several single lineages each derived from different individual donors. We used a high-throughput B-cell culture method to isolate neutralizing antibodies from an HIV-1-infected donor with high serum neutralization breadth. Clonal relatives from three distinct antibody lineages were isolated. Each of these antibody lineages displayed modest breadth and potency but shared several characteristics with the well-characterized glycan-V3 antibodies, including dependence on glycans N332 and N301, VH4 family gene utilization, a heavy chain complementarity-determining region 2 (CDRH2) insertion, and a longer-than-average CDRH3. In contrast to previously described glycan-V3 antibodies, these antibodies preferentially recognized the native Env trimer compared to monomeric gp120. These data indicate the diversity of antibody specificities that target the glycan-V3 site. The quaternary binding preference of these antibodies suggests that that their elicitation likely requires the presentation of a native-like trimeric Env immunogen.

IMPORTANCE - Broadly neutralizing antibodies targeting the HIV-1 glycan-V3 region with single lineages from individual donors have been described previously. Here we describe three lineages from a single donor, each of which targets glycan-V3. Unlike previously described glycan-V3 antibodies, these mature antibodies bind preferentially to the native Env trimer and weakly to the gp120 monomer. These data extend our knowledge of the immune response recognition of the N332 supersite region and suggest that the mode of epitope recognition is more complex than previously anticipated.

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

MeSH Terms (17)

AIDS Vaccines Amino Acid Sequence Antibodies, Monoclonal Antibodies, Neutralizing Antibody Specificity B-Lymphocytes Binding Sites Cells, Cultured Epitope Mapping HIV-1 HIV Antibodies HIV Envelope Protein gp120 HIV Infections Humans Neutralization Tests Peptide Fragments Protein Structure, Quaternary

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