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

Jaime S.Rosa Duque ¹Samuel M.S.Cheng ²Carolyn A.Cohen ³Daniel Leung ¹Xiwei Wang ¹Xiaofeng Mu ¹Yuet Chung ¹Tsun Ming Lau ¹Manni Wang ¹Wenyue Zhang ¹Yanmei Zhang ¹Howard H.W.Wong ¹Leo C.H.Tsang ²Sara Chaothai ²Tsz Chun Kwan ²John K.C.Li ²Karl C.K.Chan ²Leo L.H.Luk ²Jenson C.H.Ho ²Wing Yan Li ¹Amos M.T.Lee ¹Jennifer H.Y.Lam ¹Sau Man Chan ¹Wilfred H.S.Wong ¹Issan Y.S.Tam ¹Masashi Mori ⁴Sophie A.Valkenburg ⁵Malik Peiris ⁶Wenwei Tu ¹Yu Lung Lau¹

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作者信息

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. School of Public Health,The University of Hong Kong,Hong Kong,China;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. School of Public Health,The University of Hong Kong,Hong Kong,China;HKU-Pasteur Research Pole,School of Public Health,The University of Hong Kong,Hong Kong,China;Department of Microbiology and Immunology,Peter Doherty Institute for Infection,and Immunity,University of Melbourne,Melbourne,VIC,Australia
6. School of Public Health,The University of Hong Kong,Hong Kong,China;Center for Immunology and Infection C2i,Hong Kong,China
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Abstract

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is neces-sary.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(IM-CCC 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 Fcγ receptor 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 SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Key words

CoronaVac/Coronavirus disease 2019/Immunity/Intradermal/Vaccine

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基金项目

Health and Medical Research Fund Commissioned Research on the Novel Coronavirus Disease(COVID-19)

Hong Kong SAR(COVID190115)

Themebased Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region,China(T11-712/19-N)

Themebased Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region,China(T11-705/21-N)

出版年

2024

世界儿科杂志(英文版)

CSTPCD

ISSN：

参考文献量53

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