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| Item Type: | Article |
|---|---|
| Title: | Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization |
| Creators Name: | Turner, H.L. and Andrabi, R. and Cottrell, C.A. and Richey, S.T. and Song, G. and Callaghan, S. and Anzanello, F. and Moyer, T.J. and Abraham, W. and Melo, M. and Silva, M. and Scaringi, N. and Rakasz, E.G. and Sattentau, Q.J. and Irvine, D.J. and 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 |
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