Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is litt...Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as int...Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.展开更多
We examine Africa's vaccine manufacturing potential,spurred by the coronavirus disease 2019(COVID-19)pan-demic,while critically analyzing vaccine price inequities and procurement strategies during the pandemic,wit...We examine Africa's vaccine manufacturing potential,spurred by the coronavirus disease 2019(COVID-19)pan-demic,while critically analyzing vaccine price inequities and procurement strategies during the pandemic,with anticipation of future outbreaks.Although Africa consumes approximately 25%of the global vaccine supply,over 99%of these vaccines are produced outside the continent,primarily due to insufficient local investment.Vaccine procurement strategies have relied heavily on pooled procurement mechanisms and tiered-pricing mod-els,predominantly controlled by external organizations.Significant disparities in vaccine pricing have resulted in vaccine price inequities,with evidence suggesting price discrimination,where different prices are charged for the same vaccine across countries and regions.While vaccine prices are only one component of vaccination cam-paign costs,the inequitable pricing of vaccines poses serious challenges to fair access,especially in low-income countries.Given the inevitability of future pandemics and other outbreaks,the central question remains:Does Africa possess the capacity to strengthen its vaccine production infrastructure and reduce dependency on ex-ternal suppliers?Our review reveals that,with robust political commitment,enhanced investment in Research and Development,and leveraging the heterogeneous nature of the regional bloc,Africa has made strides toward establishing vaccine manufacturing hubs with the potential for substantial capacity expansion.Furthermore,we argue for a regional campaign based on the principles of the fair priority model as an ethical framework for vaccine procurement,which prioritizes need and ensures equitable distribution,thereby complementing existing pooled procurement arrangements in times of future pandemics.This paper concludes with two key recommen-dations based on lessons learned from the COvID-19 crisis and future preparedness.First,Africa must push for a transparent and equitable tiered-pricing structure to ensure affordability for all Second,inten展开更多
基金supported by the National Key R&D Program of China(2020YFC0849700)the Program of Chinese Academy of Medicine Sciencethe Major Science and Technology Special Projects of Yunnan Province。
文摘Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
基金the research grants COVID19F12,COVID19F10 and COVID19F02 awarded to LYL by the Health Bureau of the Government of Hong Kong,whilst TIYS was partly supported by a donation in memory of Ton Lung Quong and Reverend Marion QuongThe research work was supported additionally by grants from the Health and Medical Research Fund Commissioned Research on the Novel Coronavirus Disease(COVID-19)+1 种基金Hong Kong SAR(COVID190115)and the Theme-based Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region,China(T11-712/19-N and T11-705/21-N)The funding sources were not involved in the study design,data collection,laboratory assays,statistical computation,interpretation,or final conclusions of this project.
文摘Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.
文摘We examine Africa's vaccine manufacturing potential,spurred by the coronavirus disease 2019(COVID-19)pan-demic,while critically analyzing vaccine price inequities and procurement strategies during the pandemic,with anticipation of future outbreaks.Although Africa consumes approximately 25%of the global vaccine supply,over 99%of these vaccines are produced outside the continent,primarily due to insufficient local investment.Vaccine procurement strategies have relied heavily on pooled procurement mechanisms and tiered-pricing mod-els,predominantly controlled by external organizations.Significant disparities in vaccine pricing have resulted in vaccine price inequities,with evidence suggesting price discrimination,where different prices are charged for the same vaccine across countries and regions.While vaccine prices are only one component of vaccination cam-paign costs,the inequitable pricing of vaccines poses serious challenges to fair access,especially in low-income countries.Given the inevitability of future pandemics and other outbreaks,the central question remains:Does Africa possess the capacity to strengthen its vaccine production infrastructure and reduce dependency on ex-ternal suppliers?Our review reveals that,with robust political commitment,enhanced investment in Research and Development,and leveraging the heterogeneous nature of the regional bloc,Africa has made strides toward establishing vaccine manufacturing hubs with the potential for substantial capacity expansion.Furthermore,we argue for a regional campaign based on the principles of the fair priority model as an ethical framework for vaccine procurement,which prioritizes need and ensures equitable distribution,thereby complementing existing pooled procurement arrangements in times of future pandemics.This paper concludes with two key recommen-dations based on lessons learned from the COvID-19 crisis and future preparedness.First,Africa must push for a transparent and equitable tiered-pricing structure to ensure affordability for all Second,inten
