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展示在乙肝表面抗原(HBsAg)病毒样颗粒上的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)受体结合域可在猕猴中引发保护性免疫。

SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

作者信息

Dalvie Neil C, Tostanoski Lisa H, Rodriguez-Aponte Sergio A, Kaur Kawaljit, Bajoria Sakshi, Kumru Ozan S, Martinot Amanda J, Chandrashekar Abishek, McMahan Katherine, Mercado Noe B, Yu Jingyou, Chang Aiquan, Giffin Victoria M, Nampanya Felix, Patel Shivani, Bowman Lesley, Naranjo Christopher A, Yun Dongsoo, Flinchbaugh Zach, Pessaint Laurent, Brown Renita, Velasco Jason, Teow Elyse, Cook Anthony, Andersen Hanne, Lewis Mark G, Camp Danielle L, Silverman Judith Maxwell, Nagar Gaurav S, Rao Harish D, Lothe Rakesh R, Chandrasekharan Rahul, Rajurkar Meghraj P, Shaligram Umesh S, Kleanthous Harry, Joshi Sangeeta B, Volkin David B, Biswas Sumi, Love J Christopher, Barouch Dan H

机构信息

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Sci Adv. 2022 Mar 18;8(11):eabl6015. doi: 10.1126/sciadv.abl6015. Epub 2022 Mar 16.

DOI:10.1126/sciadv.abl6015
PMID:35294244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8926328/
Abstract

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>10) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (3.4 log) and nasal mucosa (2.9 log) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.

摘要

由于供应不足、成本高昂和储存要求,低收入和中等收入国家中获得授权的抗SARS-CoV-2疫苗仍然较少。使用广泛可用的安全佐剂(如明矾和蛋白质亚基)的新型疫苗仍可能有益于全球免疫,这些佐剂适合在现有生产设施中进行低成本生产。在此,一种包含SARS-CoV-2受体结合域-乙型肝炎表面抗原病毒样颗粒的临床阶段候选疫苗在食蟹猕猴中引发了保护性免疫。该候选疫苗诱导的中和抗体滴度(>10)高于非人灵长类动物中其他已获许可疫苗的保护范围。包含CpG 1018并未显著改善免疫反应。与假手术对照组相比,用SARS-CoV-2攻击的接种动物在支气管肺泡灌洗(约3.4 log)和鼻粘膜(约2.9 log)中的病毒载量中位数降低。这些数据支持了这种设计对于SARS-CoV-2以及其他关注变体或β冠状病毒的低成本模块化疫苗平台的潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/7a635b0a562a/sciadv.abl6015-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/41cc8b4e4b8a/sciadv.abl6015-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/aa67a0a82f49/sciadv.abl6015-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/7a635b0a562a/sciadv.abl6015-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/41cc8b4e4b8a/sciadv.abl6015-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/aa67a0a82f49/sciadv.abl6015-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/284a/8926328/7a635b0a562a/sciadv.abl6015-f3.jpg

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