A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine.
A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine.
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DOI：
10.3389/fimmu.2021.729189
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wong PT
中科院分区：
文献类型：
--
作者：
Jangra S;Landers JJ;Rathnasinghe R;O'Konek JJ;Janczak KW;Cascalho M;Kennedy AA;Tai AW;Baker JR Jr;Schotsaert M;Wong PT
几种SARS-CoV-2疫苗已获得EUA，但许多问题仍未解决，包括赋予免疫力的持续时间和交叉保护的广度。增强和塑造适应性免疫反应的佐剂，赋予对SARS-CoV-2变体的广泛保护，将是长期保护的关键，因为漂移变体不断出现。我们开发了一种鼻内、合理设计的佐剂，其整合了激活TLR和NLRP 3的纳米乳剂（NE）与RIG-I的RNA激动剂（IVT DI）。与刺突蛋白抗原的组合佐剂在小鼠中引起对SARS-CoV-2的强烈应答，对同源SARS-CoV-2和具有B1.1.7、B.1.351和P.1变体共有的N501 Y突变的变体具有显著增强的TH 1偏向性细胞应答和高病毒中和抗体滴度。此外，疫苗诱导的抗体的被动转移保护幼稚小鼠免受异源病毒攻击。NE/IVT DI使粘膜接种成为可能，并有可能改善各种SARS-CoV-2候选疫苗的免疫特征，以提供有效的交叉保护，防止未来的漂移变体。
Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.
影响因子：
4.8
作者：
Passmore C;Makidon PE;O'Konek JJ;Zahn JA;Pannu J;Hamouda T;Bitko V;Myc A;Lukacs NW;Fattom A;Baker JR Jr
通讯作者：
Baker JR Jr