@article{oai:kanazawa-u.repo.nii.ac.jp:00061032, author = {坂本, 明彦 and 水野, 哲志 and 伊從, 光洋 and 吉田, 栄人 and Sakamoto, Akihiko and Osawa, Hiroaki and Hashimoto, Hinata and Mizuno, Tetsushi and Hasyim, Ammar A. and Abe, Yu-ichi and Okahashi, Yuto and Ogawa, Ryohei and Iyori, Mitsuhiro and Shida, Hisatoshi and Yoshida, Shigeto}, issue = {1}, journal = {Emerging Microbes & Infections}, month = {Sep}, note = {Viral vectors are a potent vaccine platform for inducing humoral and T-cell immune responses. Among the various viral vectors, replication-competent ones are less commonly used for coronavirus disease 2019 (COVID-19) vaccine development compared with replication-deficient ones. Here, we show the availability of a smallpox vaccine LC16m8Δ (m8Δ) as a replication-competent viral vector for a COVID-19 vaccine. M8Δ is a genetically stable variant of the licensed and highly effective Japanese smallpox vaccine LC16m8. Here, we generated two m8Δ recombinants: one harbouring a gene cassette encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein, named m8Δ-SARS2(P7.5-S)-HA; and one encoding the S protein with a highly polybasic motif at the S1/S2 cleavage site, named m8Δ-SARS2(P7.5-SHN)-HA. M8Δ-SARS2(P7.5-S)-HA induced S-specific antibodies in mice that persisted for at least six weeks after a homologous boost immunization. All eight analysed serum samples displayed neutralizing activity against an S-pseudotyped virus at a level similar to that of serum samples from patients with COVID-19, and more than half (5/8) also had neutralizing activity against the Delta/B.1.617.2 variant of concern. Importantly, most serum samples also neutralized the infectious SARS-CoV-2 Wuhan and Delta/B.1.617.2 strains. In contrast, immunization with m8Δ-SARS2(P7.5-SHN)-HA elicited significantly lower antibody titres, and the induced antibodies had less neutralizing activity. Regarding T-cell immunity, both m8Δ recombinants elicited S-specific multifunctional CD8+ and CD4+ T-cell responses even after just a primary immunization. Thus, m8Δ provides an alternative method for developing a novel COVID-19 vaccine., 金沢大学医薬保健研究域薬学系}, pages = {2359--2370}, title = {A replication-competent smallpox vaccine LC16m8Δ-based COVID-19 vaccine}, volume = {11}, year = {2022} }