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通过多种平台稳定的HIV-1 C亚型儿科包膜糖蛋白的设计与免疫原性

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

作者信息

Kumar Sanjeev, Del Moral-Sánchez Iván, Singh Swarandeep, Newby Maddy L, Allen Joel D, Bijl Tom P L, Vaghani Yog, Jing Liang, Ortlund Eric A, Crispin Max, Patel Anamika, Sanders Rogier W, Luthra Kalpana

机构信息

Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.

出版信息

bioRxiv. 2024 Sep 19:2024.09.14.613016. doi: 10.1101/2024.09.14.613016.

DOI:10.1101/2024.09.14.613016
PMID:39345501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11429718/
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.

摘要

有多种设计平台可用于稳定可溶性HIV-1包膜（Env）三聚体，这些三聚体可用作抗原诱饵和疫苗抗原。然而，稳定HIV-1 C亚型三聚体可能具有挑战性。在此，我们使用多种平台，包括SOSIP.v8.2、铁蛋白纳米颗粒（NP）和I53-50双组分NP，基于从一名儿科精英中和者（AIIMS_329）分离的Env稳定了HIV-1 C亚型三聚体，随后对其生物物理、抗原和免疫原性特性进行了表征。稳定的329 Env显示出与三聚体特异性HIV-1广谱中和抗体（bnAbs）的结合亲和力，与非中和抗体（非nAbs）的结合可忽略不计。负染色电子显微镜（nsEM）证实了Env的天然样构象。329 SOSIP.v8.2在铁蛋白和双组分I53-50 NPs上的多聚化提高了对HIV-1 bnAbs的总体亲和力以及在兔体内的免疫原性。这些稳定的HIV-1 C亚型329 Env显示出未来用作抗原诱饵和多价疫苗候选物组分的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/4060b9121ff0/nihpp-2024.09.14.613016v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/62eb699f87e2/nihpp-2024.09.14.613016v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/1d607720ad0e/nihpp-2024.09.14.613016v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/d870347e42b1/nihpp-2024.09.14.613016v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/4060b9121ff0/nihpp-2024.09.14.613016v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/62eb699f87e2/nihpp-2024.09.14.613016v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/1d607720ad0e/nihpp-2024.09.14.613016v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/d870347e42b1/nihpp-2024.09.14.613016v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7705/11429718/4060b9121ff0/nihpp-2024.09.14.613016v1-f0004.jpg

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