Gach, JS;
Mara, KJV;
LaBranche, CC;
van Gils, MJ;
McCoy, LE;
Klasse, PJ;
Montefiori, DC;
... Forthal, DN; + view all
(2019)
Antibody responses elicited by immunization with BG505 trimer-immune complexes.
Journal of Virology
10.1128/JVI.01188-19.
(In press).
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Abstract
Immune complex (IC) vaccines have been successfully used to increase immune responses against various pathogens, including HIV-1. Additionally, IC vaccines can induce qualitatively different antibody responses with distinct antigenic specificities compared to the same antigens used alone. Here we measured the HIV-1-specific antibody response in female New Zealand White rabbits after immunization with ICs made from BG505 SOSIP.664 trimers (BG505 trimers) and three different rabbit monoclonal antibodies (mAbs) with varying neutralization profiles. Two of the mAbs were specific for a hole in the glycan shield of the BG505 trimer while the third, which bound less avidly, was specific for determinants at the gp41/gp120 interface. We found that immunizing with one of the glycan hole-specific ICs resulted in lower levels of trimer-binding antibodies compared to vaccination with the uncomplexed trimer and that ICs made using either of the glycan hole-specific mAbs resulted in lower rates of anti-trimer antibody decay. We conclude that ICs based on mAbs that bound to the immunodominant glycan hole epitope likely diverted antibody responses, to some extent, away from this site and to other regions of the trimer. However, this outcome was not accompanied by a widening of the breadth or an increase in the potency of neutralizing antibody responses compared with uncomplexed trimers.
| Type: | Article |
|---|---|
| Title: | Antibody responses elicited by immunization with BG505 trimer-immune complexes |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1128/JVI.01188-19 |
| Publisher version: | https://doi.org/10.1128/JVI.01188-19 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| 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/10079826 |
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