Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.
Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.
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DOI：
10.15252/embr.202152447
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发表时间：
2021-08-04
期刊：
影响因子：
7.7
通讯作者：
Rehwinkel J
中科院分区：
文献类型：
--
作者：
Chauveau L;Bridgeman A;Tan TK;Beveridge R;Frost JN;Rijal P;Pedroza-Pacheco I;Partridge T;Gilbert-Jaramillo J;Knight ML;Liu X;Russell RA;Borrow P;Drakesmith H;Townsend AR;Rehwinkel J
环GMP-AMP（cGAMP）是由激活STING的cGAS产生的免疫刺激分子。当与抗原一起施用时，cGAMP是佐剂。cGAMP也在出芽期间掺入包膜病毒颗粒中。在这里，我们研究是否包含病毒疫苗载体内的cGAMP增强其免疫原性。我们用含有HIV-1 Gag和水泡性口炎病毒包膜糖蛋白G（VSV-G）的病毒样颗粒（VLP）免疫小鼠。VLP的cGAMP负载增强了CD 4和CD 8 T细胞应答。它还以STING依赖性方式增加VLP-和VSV-G-特异性抗体滴度，并增强病毒中和作用，伴随着T滤泡辅助细胞数量的增加。接种含有血凝素的cGAMP负载VLP可诱导高滴度的甲型流感病毒中和抗体，并在病毒攻毒时提供保护。这需要在VLP内包含cGAMP，并且在显著降低的cGAMP剂量下实现。类似地，含有SARS-CoV-2刺突蛋白的VLP的cGAMP负载增强刺突特异性抗体滴度。因此，载有cGAMP的VLP是一种有吸引力的疫苗接种平台。cGAMP是一种环状二核苷酸，是一种佐剂并激活STING。这项研究表明，设计用于将抗原和cGAMP递送至同一抗原呈递细胞的载有cGAMP的病毒样颗粒是一种有吸引力的疫苗接种平台。
Cyclic GMP‐AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus‐like particles (VLPs) containing HIV‐1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV‐G). cGAMP loading of VLPs augments CD4 and CD8 T‐cell responses. It also increases VLP‐ and VSV‐G‐specific antibody titres in a STING‐dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP‐loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS‐CoV‐2 Spike protein enhances Spike‐specific antibody titres. cGAMP‐loaded VLPs are thus an attractive platform for vaccination. cGAMP, a cyclic di‐nucleotide, is an adjuvant and activates STING. This study shows that cGAMP‐loaded virus‐like particles, designed to deliver antigen and cGAMP to the same antigen‐presenting cell, are an attractive platform for vaccination.