tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2022 Sep 7;1-40.
doi: 10.1080/22221751.2022.2122580. Online ahead of print.
A replication-competent smallpox vaccine LC16m8Δ-based COVID-19 vaccine
Akihiko Sakamoto[SUP] 1 [/SUP], Hiroaki Osawa[SUP] 1 [/SUP], Hinata Hashimoto[SUP] 1 [/SUP], Tetsushi Mizuno[SUP] 1 2 [/SUP], Ammar A Hasyim[SUP] 1 [/SUP], Yu-Ichi Abe[SUP] 1 [/SUP], Yuto Okahashi[SUP] 1 [/SUP], Ryohei Ogawa[SUP] 3 [/SUP], Mitsuhiro Iyori[SUP] 1 [/SUP], Hisatoshi Shida[SUP] 4 [/SUP], Shigeto Yoshida[SUP] 1 [/SUP]
Affiliations
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-S[SUB]HN[/SUB])-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-S[SUB]HN[/SUB])-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[SUP]+[/SUP] and CD4[SUP]+[/SUP] T-cell responses even after just a primary immunization. Thus, m8Δ provides an alternative method for developing a novel COVID-19 vaccine.
Keywords: BALB/c mouse; COVID-19; Delta/B.1.617.2 variant of concern; LC16m8; SARS-CoV-2; Subject classification codes: Emerging and Re-Emerging Coronaviruses; cellular immunity; humoral immunity; prime-boost immunization.
. 2022 Sep 7;1-40.
doi: 10.1080/22221751.2022.2122580. Online ahead of print.
A replication-competent smallpox vaccine LC16m8Δ-based COVID-19 vaccine
Akihiko Sakamoto[SUP] 1 [/SUP], Hiroaki Osawa[SUP] 1 [/SUP], Hinata Hashimoto[SUP] 1 [/SUP], Tetsushi Mizuno[SUP] 1 2 [/SUP], Ammar A Hasyim[SUP] 1 [/SUP], Yu-Ichi Abe[SUP] 1 [/SUP], Yuto Okahashi[SUP] 1 [/SUP], Ryohei Ogawa[SUP] 3 [/SUP], Mitsuhiro Iyori[SUP] 1 [/SUP], Hisatoshi Shida[SUP] 4 [/SUP], Shigeto Yoshida[SUP] 1 [/SUP]
Affiliations
- PMID: 36069348
- DOI: 10.1080/22221751.2022.2122580
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-S[SUB]HN[/SUB])-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-S[SUB]HN[/SUB])-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[SUP]+[/SUP] and CD4[SUP]+[/SUP] T-cell responses even after just a primary immunization. Thus, m8Δ provides an alternative method for developing a novel COVID-19 vaccine.
Keywords: BALB/c mouse; COVID-19; Delta/B.1.617.2 variant of concern; LC16m8; SARS-CoV-2; Subject classification codes: Emerging and Re-Emerging Coronaviruses; cellular immunity; humoral immunity; prime-boost immunization.