Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents  

作　　者：Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau 

机构地区：[1]Department of Paediatrics and Adolescent Medicine,The University of Hong Kong,Hong Kong,China [2]School of Public Health,The University of Hong Kong,Hong Kong,China [3]HKU‑Pasteur Research Pole,School of Public Health,The University of Hong Kong,Hong Kong,China [4]Research Institute for Bioresources and Biotechnology,Ishikawa Prefectural University,Nonoichi,Japan [5]Department of Microbiology and Immunology,Peter Doherty Institute for Infection,and Immunity,University of Melbourne,Melbourne,VIC,Australia [6]Center for Immunology and Infection C2i,Hong Kong,China

出　　处：《World Journal of Pediatrics》2024年第4期353-370,共18页世界儿科杂志（英文版）

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 Quong;The research work was supported additionally by grants from the Health and Medical Research Fund Commissioned Research on the Novel Coronavirus Disease(COVID-19);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.

摘　　要：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.

关 键 词：CoronaVac Coronavirus disease 2019 Immunity INTRADERMAL Vaccine 

分 类 号：R72[医药卫生—儿科]