Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute resp...Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines is to provide adequate immune protection and avoid severe disease and death.Mucosal vaccine candidates for COVID-19 including vector vaccines,recombinant subunit vaccines and live attenuated vaccines are under development.Furthermore,subunit protein vaccines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings,resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines.Additional to their ability to trigger stable,protective immune responses at the sites of pathogenic infection,the development of‘specific’mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics.However,their efficacy and safety should be confirmed.展开更多
Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respi...Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.展开更多
文摘Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or orally.The goal of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines is to provide adequate immune protection and avoid severe disease and death.Mucosal vaccine candidates for COVID-19 including vector vaccines,recombinant subunit vaccines and live attenuated vaccines are under development.Furthermore,subunit protein vaccines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings,resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines.Additional to their ability to trigger stable,protective immune responses at the sites of pathogenic infection,the development of‘specific’mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics.However,their efficacy and safety should be confirmed.
基金supported by the National Program on Key Research Project of China(2020YFC0842600)the National Natural Science Foundation of China(82041038,81871651,and 81991491)+1 种基金the Major Science and Technology Program of Fujian Province(2020YZ014001)the Natural Science Foundation of Fujian Province(2021J02006)。
文摘Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.
