Nogal, B;
McCoy, LE;
van Gils, MJ;
Cottrell, CA;
Voss, JE;
Andrabi, R;
Pauthner, M;
... Ward, AB; + view all
(2020)
HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite.
Science Advances
, 6
(23)
, Article eaba0512. 10.1126/sciadv.aba0512.
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Abstract
To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole–dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole–specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A 3.5-Å cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.v5.2 trimer demonstrated that while the epitope recognized overlapped the N332 glycan supersite by contacting the GDIR motif at the base of V3, primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway.
| Type: | Article |
|---|---|
| Title: | HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.aba0512 |
| Publisher version: | https://doi.org/10.1126/sciadv.aba0512 |
| Language: | English |
| Additional information: | 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 work is properly cited. http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10102466 |
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