Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization.
Sci Adv
; 7(31)2021 07.
Article
in English
| MEDLINE | ID: covidwho-1388435
ABSTRACT
Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Antibodies
/
HIV Infections
/
HIV-1
/
AIDS Vaccines
/
Env Gene Products, Human Immunodeficiency Virus
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
SCIADV.ABH2791
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