Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
618kB
[thumbnail of Supplementary Material]
Preview
PDF (Supplementary Material) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization
Creators Name:Turner, H.L., Andrabi, R., Cottrell, C.A., Richey, S.T., Song, G., Callaghan, S., Anzanello, F., Moyer, T.J., Abraham, W., Melo, M., Silva, M., Scaringi, N., Rakasz, E.G., Sattentau, Q.J., Irvine, D.J., Burton, D.R. and Ward, A.B.
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.
Keywords:AIDS Vaccines, COVID-19, HIV Antibodies, HIV Infections, HIV-1, Human Immunodeficiency Virus env Gene Products, SARS-CoV-2, Animals, Macaca mulatta, Rabbits
Source:Science Advances
ISSN:2375-2548
Publisher:American Association for the Advancement of Science
Volume:7
Number:31
Page Range:eabh2791
Date:July 2021
Official Publication:https://doi.org/10.1126/sciadv.abh2791
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library