An attenuated vaccinia vaccine encoding the severe acute respiratory syndrome coronavirus-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human angiotensin-converting enzyme 2 transgenic mice from severe acute respiratory syndrome coronavirus-2 and its variants

• Published in: Frontiers in microbiology Vol. 13; p. 967019
• Main Authors: Ishigaki, Hirohito, Yasui, Fumihiko, Nakayama, Misako, Endo, Akinori, Yamamoto, Naoki, Yamaji, Kenzaburo, Nguyen, Cong Thanh, Kitagawa, Yoshinori, Sanada, Takahiro, Honda, Tomoko, Munakata, Tsubasa, Higa, Masahiko, Toyama, Sakiko, Kono, Risa, Takagi, Asako, Matsumoto, Yusuke, Koseki, Aya, Hayashi, Kaori, Shiohara, Masanori, Ishii, Koji, Saeki, Yasushi, Itoh, Yasushi, Kohara, Michinori
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 18.11.2022
• Subjects: animal model; broad immune response; DIs-based SARS-CoV-2 vaccine; durable immune response; Microbiology; SARS-CoV-2; SARS-CoV-2 variants
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2022.967019

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2   S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants.