tetano
Editor, Senior Moderator
EBioMedicine
. 2021 Dec 20;75:103762.
doi: 10.1016/j.ebiom.2021.103762. Online ahead of print.
Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models
Runhong Zhou[SUP] 1 [/SUP], Pui Wang[SUP] 2 [/SUP], Yik-Chun Wong[SUP] 1 [/SUP], Haoran Xu[SUP] 1 [/SUP], Siu-Ying Lau[SUP] 2 [/SUP], Li Liu[SUP] 3 [/SUP], Bobo Wing-Yee Mok[SUP] 4 [/SUP], Qiaoli Peng[SUP] 5 [/SUP], Na Liu[SUP] 1 [/SUP], Kin-Fai Woo[SUP] 1 [/SUP], Shaofeng Deng[SUP] 2 [/SUP], Rachel Chun-Yee Tam[SUP] 2 [/SUP], Haode Huang[SUP] 1 [/SUP], Anna Jinxia Zhang[SUP] 4 [/SUP], Dongyan Zhou[SUP] 6 [/SUP], Biao Zhou[SUP] 1 [/SUP], Chun-Yin Chan[SUP] 1 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Dawei Yang[SUP] 1 [/SUP], Ka-Kit Au[SUP] 1 [/SUP], Kwok-Yung Yuen[SUP] 7 [/SUP], Honglin Chen[SUP] 8 [/SUP], Zhiwei Chen[SUP] 9 [/SUP]
Affiliations
Abstract
Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal.
Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2.
Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity.
Interpretation: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems.
Funding: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.
Keywords: Live-attenuated influenza-based vaccine; Mucosal immunity; Nasal prevention; PD1-based DNA vaccine; Receptor binding domain; SARS-CoV-2.
. 2021 Dec 20;75:103762.
doi: 10.1016/j.ebiom.2021.103762. Online ahead of print.
Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models
Runhong Zhou[SUP] 1 [/SUP], Pui Wang[SUP] 2 [/SUP], Yik-Chun Wong[SUP] 1 [/SUP], Haoran Xu[SUP] 1 [/SUP], Siu-Ying Lau[SUP] 2 [/SUP], Li Liu[SUP] 3 [/SUP], Bobo Wing-Yee Mok[SUP] 4 [/SUP], Qiaoli Peng[SUP] 5 [/SUP], Na Liu[SUP] 1 [/SUP], Kin-Fai Woo[SUP] 1 [/SUP], Shaofeng Deng[SUP] 2 [/SUP], Rachel Chun-Yee Tam[SUP] 2 [/SUP], Haode Huang[SUP] 1 [/SUP], Anna Jinxia Zhang[SUP] 4 [/SUP], Dongyan Zhou[SUP] 6 [/SUP], Biao Zhou[SUP] 1 [/SUP], Chun-Yin Chan[SUP] 1 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Dawei Yang[SUP] 1 [/SUP], Ka-Kit Au[SUP] 1 [/SUP], Kwok-Yung Yuen[SUP] 7 [/SUP], Honglin Chen[SUP] 8 [/SUP], Zhiwei Chen[SUP] 9 [/SUP]
Affiliations
- PMID: 34942445
- PMCID: PMC8687884
- DOI: 10.1016/j.ebiom.2021.103762
Abstract
Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal.
Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2.
Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity.
Interpretation: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems.
Funding: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.
Keywords: Live-attenuated influenza-based vaccine; Mucosal immunity; Nasal prevention; PD1-based DNA vaccine; Receptor binding domain; SARS-CoV-2.