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bioRxiv · 10.1101/2024.09.14.613016

Design and immunogenicity of an HIV-1 clade C pediatric envelope glycoprotein stabilized by multiple platforms

Kumar, S.·del Moral-Sanchez, I.·Singh, S.·Newby, M. L.·Allen, J. D.·Bijl, T. P.·Vaghani, Y.·Jing, L.·Ortlund, E. A.·Crispin, M.·Patel, A.·Sanders, R. W.·Luthra, K.
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Abstract

Various design platforms are available to stabilize soluble HIV-1 envelope (Env) trimers, which can be used as antigenic baits and vaccine antigens. However, stabilizing HIV-1 clade C trimers can be challenging. Here, we stabilized an HIV-1 clade C trimer based on an Env isolated from a pediatric elite-neutralizer (AIIMS_329) using multiple platforms, including SOSIP.v8.2, ferritin nanoparticles (NP) and an I53-50 two-component NP, followed by characterization of their biophysical, antigenic, and immunogenic properties. The stabilized 329 Envs showed binding affinity to trimer-specific HIV-1 broadly neutralizing antibodies (bnAbs), with negligible binding to non-neutralizing antibodies (non-nAbs). Negative-stain electron microscopy (nsEM) confirmed the native-like conformation of the Envs. Multimerization of 329 SOSIP.v8.2 on ferritin and two-component I53-50 NPs improved the overall affinity to HIV-1 bnAbs and immunogenicity in rabbits. These stabilized HIV-1 clade C 329 Envs demonstrate the potential to be used as antigenic baits and as components of multivalent vaccine candidates in future.

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Kumar, S., del Moral-Sanchez, I., Singh, S., Newby, M. L., Allen, J. D., Bijl, T. P., Vaghani, Y., Jing, L., Ortlund, E. A., Crispin, M., Patel, A., Sanders, R. W., Luthra, K.. 2024-09-19. Design and immunogenicity of an HIV-1 clade C pediatric envelope glycoprotein stabilized by multiple platforms. https://doi.org/10.1101/2024.09.14.613016

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