tetano
Editor, Senior Moderator
Sci Rep
. 2026 Jun 13.
doi: 10.1038/s41598-026-55581-y. Online ahead of print.
Development of a recombinant single-cycle influenza viral vector as an intranasal vaccine against SARS-CoV-2
Jonathan Munro[SUP] 1 [/SUP], Diana Melnyk[SUP] 1 [/SUP], Madeeha Afzal[SUP] 2 [/SUP], Lisa Schimanski[SUP] 1 [/SUP], Alexander A Cohen[SUP] 3 [/SUP], Jennifer R Keeffe[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 3 [/SUP], William S James[SUP] 2 [/SUP], Alain R Townsend[SUP] 4 5 [/SUP], Tiong Kit Tan[SUP] 6 7 [/SUP]
Affiliations
The COVID-19 pandemic has demonstrated the detrimental potential of zoonotic coronavirus transmission to human populations. Effective vaccines capable of eliciting immunity to SARS-CoV-2 have been pivotal in mitigating the spread of the virus. In this study, we describe the generation of a non-replicating pseudotyped influenza A virus (S-FLU), where the native haemagglutinin (HA) sequence is replaced with the coding sequence of either a membrane-anchored form (TM) or secretory form (Sec) of the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 Wuhan (S-RBD Wuhan). We showed that both S-RBD-TM and S-RBD-Sec viruses can be generated via reverse genetics and grown to high titre. Intranasal immunisation in mice with S-RBD-TM elicits robust serum binding and neutralisation activity against SARS-CoV-2, superior to S-RBD-Sec. Furthermore, we demonstrate that a heterologous prime-boost immunisation regimen in mice with S-RBD-TM Wuhan and S-RBD-TM BM48-31 (a distant Clade 3 SARS-like betacoronavirus (sarbecovirus)) increases antibody binding breadth against mismatched sarbecoviruses compared to homologous prime-boost with S-RBD-TM Wuhan, although this did not translate into significantly enhanced cross-neutralisation across the tested virus panel. These results demonstrate that S-RBD delivery via the intranasal route induces both systemic and mucosal antibody responses and provide a foundation for further optimisation of S-RBD sarbecovirus vaccine strategies.
Keywords: Influenza; Non-replicating viral vector; SARS-CoV-2; Vaccine.
. 2026 Jun 13.
doi: 10.1038/s41598-026-55581-y. Online ahead of print.
Development of a recombinant single-cycle influenza viral vector as an intranasal vaccine against SARS-CoV-2
Jonathan Munro[SUP] 1 [/SUP], Diana Melnyk[SUP] 1 [/SUP], Madeeha Afzal[SUP] 2 [/SUP], Lisa Schimanski[SUP] 1 [/SUP], Alexander A Cohen[SUP] 3 [/SUP], Jennifer R Keeffe[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 3 [/SUP], William S James[SUP] 2 [/SUP], Alain R Townsend[SUP] 4 5 [/SUP], Tiong Kit Tan[SUP] 6 7 [/SUP]
Affiliations
- PMID: 42288524
- DOI: 10.1038/s41598-026-55581-y
The COVID-19 pandemic has demonstrated the detrimental potential of zoonotic coronavirus transmission to human populations. Effective vaccines capable of eliciting immunity to SARS-CoV-2 have been pivotal in mitigating the spread of the virus. In this study, we describe the generation of a non-replicating pseudotyped influenza A virus (S-FLU), where the native haemagglutinin (HA) sequence is replaced with the coding sequence of either a membrane-anchored form (TM) or secretory form (Sec) of the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 Wuhan (S-RBD Wuhan). We showed that both S-RBD-TM and S-RBD-Sec viruses can be generated via reverse genetics and grown to high titre. Intranasal immunisation in mice with S-RBD-TM elicits robust serum binding and neutralisation activity against SARS-CoV-2, superior to S-RBD-Sec. Furthermore, we demonstrate that a heterologous prime-boost immunisation regimen in mice with S-RBD-TM Wuhan and S-RBD-TM BM48-31 (a distant Clade 3 SARS-like betacoronavirus (sarbecovirus)) increases antibody binding breadth against mismatched sarbecoviruses compared to homologous prime-boost with S-RBD-TM Wuhan, although this did not translate into significantly enhanced cross-neutralisation across the tested virus panel. These results demonstrate that S-RBD delivery via the intranasal route induces both systemic and mucosal antibody responses and provide a foundation for further optimisation of S-RBD sarbecovirus vaccine strategies.
Keywords: Influenza; Non-replicating viral vector; SARS-CoV-2; Vaccine.