Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.
Nat Commun. 2020 Nov 30;11(1):6121. doi: 10.1038/s41467-020-19819-1.
Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.
改良安卡拉痘苗病毒（MVA）是一种高度减毒的痘病毒载体，广泛用于开发传染病和癌症疫苗。我们展示了一种基于独特三质粒系统的疫苗平台的构建，该平台可从化学合成 DNA 中高效生成重组 MVA 载体。针对由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的全球大流行，我们使用该疫苗平台快速生产共表达 SARS-CoV-2 刺突和核衣壳抗原的完全合成 MVA（sMVA）载体，这两种免疫优势抗原与保护性免疫有关。我们表明，用这些 sMVA 载体免疫的小鼠会产生针对 SARS-CoV-2 抗原的强大体液和细胞免疫应答，包括有效的中和抗体。这些结果表明，基于合成 DNA 的疫苗平台具有高效生成重组 MVA 载体和快速开发基于多抗原痘病毒的 SARS-CoV-2 疫苗候选物的潜力。
