A replication-competent smallpox vaccine LC16m8Δ-based COVID-19 vaccine. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Sakamoto, Akihiko; Osawa, Hiroaki; Hashimoto, Hinata; Mizuno, Tetsushi; Hasyim, Ammar A.; Abe, Yu-ichi; Okahashi, Yuto; Ogawa, Ryohei; Iyori, Mitsuhiro; Shida, Hisatoshi; Yoshida, Shigeto
• Is Part Of: Emerging microbes & infections. Volume 11:Issue 1(2022)
• Page Start: 2359
• Page End: 2370
• Publication Date: 2022-12-31
• Subjects: BALB/c mouse -- cellular immunity -- COVID-19 -- Delta/B.1.617.2 variant of concern -- humoral immunity -- LC16m8 -- prime-boost immunization -- SARS-CoV-2; emerging and re-Emerging coronaviruses; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2022.2122580
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: 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.