Adenovirus-vectored SARS-CoV-2 vaccine expressing S1-N fusion protein.
Adenovirus-vectored SARS-CoV-2 vaccine expressing S1-N fusion protein.
复制标题
表达S1-N融合蛋白的腺病毒载体SARS-CoV-2疫苗。
DOI：
10.1093/abt/tbac015
复制
发表时间：
2022-07
影响因子：
--
通讯作者：
Gambotto, Andrea
中科院分区：
文献类型：
--
作者：
Khan, Muhammad S;Kim, Eun;McPherson, Alex;Weisel, Florian J;Huang, Shaohua;Kenniston, Thomas W;Percivalle, Elena;Cassaniti, Irene;Baldanti, Fausto;Meisel, Marlies;Gambotto, Andrea
为了全球疫苗公平，需要额外的安全和免疫原性的COVID-19疫苗。我们构建了一个SARS-CoV-2 S1亚单位抗原和核衣壳蛋白的重组5型腺病毒载体（Ad 5.SARS-CoV-2-S1 N）。用Ad 5.SARS-CoV-2-S1 N单次皮下免疫诱导了与单独编码S1的重组5型腺病毒载体（Ad 5.SARS-CoV-2-S1）相似的体液应答，沿着显著更高的S1特异性细胞应答。免疫原性通过同源初免-加强疫苗接种得到改善，并且通过使用亚单位重组S1蛋白的肌内异源初免-加强疫苗接种得到进一步改善。低剂量预充（1 × 1010 v. p.）SARS-CoV-2-S1 N和用野生型重组rS 1或B.1.351重组rS 1加强免疫诱导了强有力的中和反应，该反应对β和γ SARS-CoV-2变体持续存在。这种新型的Ad 5载体SARS-CoV-2疫苗候选物在小鼠中显示出有希望的免疫原性，并支持进一步开发基于COVID-19的疫苗，将核蛋白作为靶抗原。重要性声明：由于免疫逃避性SARS-CoV-2变体的出现，针对刺突外抗原的SARS-CoV-2疫苗的研究是下一代SARS-CoV-2疫苗的兴趣点。这项工作是第一次发表的调查刺突和核蛋白融合疫苗抗原。
Additional COVID-19 vaccines that are safe and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2 S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N). A single subcutaneous immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime-boost vaccination, and further improved through intramuscular heterologous prime-boost vaccination using subunit recombinant S1 protein. Priming with low dose (1 × 1010 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wild-type recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, which was sustained against Beta and Gamma SARS-CoV-2 variants. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19-based vaccines incorporating the nucleoprotein as a target antigen. Statement of Significance: Investigation of SARS-CoV-2 vaccines targeting antigens outside of spike is a point of interest for next-generation SARS-CoV-2 vaccines due to the emergence of immune evasive SARS-CoV-2 variants. This work represents the first published investigation of a spike and nucleoprotein fusion vaccine antigen.