Neutralizing antibodies induced by first-generation gp41-stabilized HIV-1 envelope trimers and nanoparticles

Kumar, S.; Lin, X.; Ngo, T.; Shapero, B. A.; Sou, C.; Allen, J. D.; Copps, J.; Zhang, L.; Ozorowski, G.; He, L.; Crispin, M.; Ward, A. B.; Wilson, I. A.; Zhu, J.

doi:10.1101/2020.12.02.408328

bioRxiv · 10.1101/2020.12.02.408328

Neutralizing antibodies induced by first-generation gp41-stabilized HIV-1 envelope trimers and nanoparticles

Kumar, S.·Lin, X.·Ngo, T.·Shapero, B. A.·Sou, C.·Allen, J. D.·Copps, J.·Zhang, L.·Ozorowski, G.·He, L.·Crispin, M.·Ward, A. B.·Wilson, I. A.·Zhu, J.

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Abstract

Antigen-specific B-cell sorting and next-generation sequencing (NGS) were combined to isolate HIV-1 neutralizing antibodies (NAbs) from mice and rabbits immunized with BG505 trimers and nanoparticles. Three mouse NAbs potently neutralize BG505.T332N and recognize a glycan epitope centered at the C3/V4 region, as revealed by electron microscopy (EM), x-ray crystallography, and epitope mapping. Three potent NAbs were sorted from rabbit B cells that target glycan holes on the BG505 envelope glycoprotein (Env) and account for a significant portion of autologous NAb response. We then determined a 3.4[A]-resolution crystal structure for the clade C transmitted/founder Du172.17 Env with a redesigned heptad repeat 1 (HR1) bend. This clade C Env, as a soluble trimer and attached to a ferritin nanoparticle, along with a clade A Q482-d12 Env trimer, elicited distinct NAb responses in rabbits. Our study demonstrates that nanoparticles presenting gp41-stabilized trimers can induce potent NAb responses in mice and rabbits with Env-dependent breadth. TEASERMouse and rabbit NAbs elicited by gp41-stabilized trimers and nanoparticles neutralize autologous HIV-1 by targeting different epitopes

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Kumar, S., Lin, X., Ngo, T., Shapero, B. A., Sou, C., Allen, J. D., Copps, J., Zhang, L., Ozorowski, G., He, L., Crispin, M., Ward, A. B., Wilson, I. A., Zhu, J.. 2020-12-02. Neutralizing antibodies induced by first-generation gp41-stabilized HIV-1 envelope trimers and nanoparticles. https://doi.org/10.1101/2020.12.02.408328

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