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Antibody Responses Elicited by Immunization with BG505 Trimer Immune Complexes
Johannes S Gach1, Kane J V Mara1, Celia C LaBranche2
1Department of Medicine, University of California Irvine, School of Medicine, Irvine, California, USA.
Journal of Virology
|August 4, 2019
Summary
Immune complex (IC) vaccines using HIV-1 trimers and antibodies showed they could slow antibody decay. However, this method did not broaden or increase the potency of neutralizing antibody responses compared to uncomplexed trimers.
Area of Science:
- Immunology and Vaccinology
- Structural Biology of Viruses
Background:
- Immune complex (IC) vaccines can enhance immune responses and alter antibody specificities compared to conventional antigen delivery.
- HIV-1 trimers (BG505 SOSIP.664) present immunodominant glycan holes that may suppress responses to other critical epitopes.
- Monoclonal antibodies (MAbs) targeting specific epitopes can be used to form ICs for vaccine development.
Purpose of the Study:
- To investigate if ICs formed with BG505 trimers and MAbs targeting glycan holes can redirect antibody responses away from immunodominant sites.
- To evaluate the impact of IC vaccination on the breadth, potency, and decay kinetics of HIV-1-specific antibody responses.
- To explore the potential of IC vaccination to improve vaccine-induced antibody duration.
Main Methods:
- Female New Zealand White rabbits were immunized with ICs composed of BG505 trimers and three rabbit MAbs with distinct binding profiles.
- Two MAbs targeted glycan holes, while one targeted the gp41-gp120 interface.
- HIV-1-specific antibody responses, including binding antibody levels, decay rates, and neutralizing antibody breadth and potency, were measured.
Main Results:
- Immunization with glycan-hole-specific ICs resulted in lower levels of trimer-binding antibodies compared to uncomplexed trimers.
- ICs formed with glycan-hole-specific MAbs led to slower decay rates of anti-trimer antibodies.
- IC vaccination did not increase the breadth or potency of neutralizing antibody responses compared to uncomplexed trimers.
Conclusions:
- ICs targeting immunodominant glycan holes on BG505 trimers did not effectively dampen these epitopes or broaden neutralizing responses.
- IC vaccination may offer a strategy to increase the duration of vaccine-induced antibody responses.
- Selective epitope dampening of HIV-1 trimers using ICs appears to be largely ineffective in enhancing protective immunity.
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