Humoral and Cellular Immunogenicity and Safety of 3-Dose Inactivated COVID-19 Vaccine in Young Children Less Than 5 Years With Kidney Diseases

There is no available data pertaining to humoral and cellular response against COVID-19 among young children with kidney diseases following inactivated vaccine.1Han B. Song Y. Li C. Yang W. Ma Q. Jiang Z. Li M. Lian X. Jiao W. Wang L. et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.Lancet Infect Dis. 2021; 21: 1645-1653https://doi.org/10.1016/S1473-3099(21)00319-4Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar We therefore evaluated the immunogenicity and safety of 3-dose CoronaVac at an accelerated schedule (0.5ml; day 0, 14, 28) in a prospective study in Hong Kong (COVAC; NCT04800133) (Supplementary Methods).2Ma A.L.-T. Leung D. Chan E.Y.-H. Chim S. Cheng S. Ho F.T.-W. Lai W.-M. Tong P.-C. Lee M.H.-L. Wong W.H.-S. et al.Antibody responses to 2 doses of mRNA COVID-19 vaccine in pediatric patients with kidney diseases.Kidney International. 2022; 101: 1069-1072Abstract Full Text Full Text PDF Scopus (6) Google Scholar Sixty-four children were enrolled and five young children (median age 3.3 years, IQR 3.1-3.6; 3 females; 3 Chinese) were analyzed (glomerular disease on immunosuppression, n=2; aCKD, n=2; kidney failure, n=1). (Table S1) We tracked antibody responses in our patients against wild-type (WT) SARS-CoV-2, including S-RBD IgG for binding antibody and surrogate virus neutralization test (sVNT) for neutralization longitudinally from pre-vaccine baseline to post-dose 3 (Fig. 1A and 1B).3Rosa Duque J.S. Wang X. Leung D. Cheng S.M.S. Cohen C.A. Mu X. Hachim A. Zhang Y. Chan S.M. Chaothai S. et al.Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents.Nat Commun. 2022; 13: 3700https://doi.org/10.1038/s41467-022-31485-zCrossref PubMed Scopus (18) Google Scholar After 3 doses, all were seropositive for S-RBD IgG and had a high geometric mean sVNT% level of 94.0%, with increases in titers following successive doses. We also studied IFN-γ+ antiviral CD4+ helper and CD8+ cytotoxic T-cell responses against SARS-CoV-2 S, N and M proteins (Fig. 2). We detected a significant increase of SNM-specific IFN-γ+ CD4+ T-cell response in all 5 patients (Fig. 2B). Other T-cell responses such as IL-2 also showed an increasing trend (Fig. S1A-D). Importantly, all demonstrated S-specific or SNM-specific IFN-γ+ CD4+ and CD8+ T-cell responses. When compared with WT antibody response, we found a significantly lower sVNT% level against Omicron BA.1 (post-dose 3, 94.0% vs 17.9%, P=0.0012) (Fig. S2A), indicating partial neutralization escape. Nonetheless, IFN-γ+ T-cell responses were similar between Omicron BA.1 and WT (Fig. S2B-D).4Leung D. Cohen C.A. Mu X. Rosa Duque J.S. Cheng S.M.S. Wang X. Wang M. Zhang W. Zhang Y. Tam I.Y.S. et al.Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents.Front Immunol. 2023; 141106837https://doi.org/10.3389/fimmu.2023.1106837Crossref Scopus (0) Google Scholar In addition, we noticed comparable antibody responses between these 5 patients and healthy subjects aged 3-5 who were recruited in another subgroup of the same prospective study (Fig. S3A-B). We also found that CoronaVac was safe and tolerable in our patients, and no breakthrough infections were reported following a median of 118 days (IQR 111-132 days) after dose 3 (Supplemental text 1 and Fig. S4). In conclusion, we demonstrated that accelerated, 3-dose CoronaVac vaccination was safe, and elicited satisfactory antibody and T-cell responses in young children with kidney diseases. T-cell responses appeared preserved against Omicron BA.1, which prevent severe COVID-19. The authors declare no conflicts of interest. Y.L. Lau conceptualized the study. Y.L. Lau, M. Peiris, W. Tu, D. Leung, J.S. Rosa Duque, and X. Mu designed the study. Y.L. Lau led the acquisition of funding. Y.L. Lau, W. Tu, and M. Peiris supervised the project. S.M. Chan, D. Leung, X. Mu, S.M.S. Cheng, I.Y.S. Tam, and J.H.Y. Lam led the study administrative procedures. A.L.T. Ma, Y.L. Lau, J.S. Rosa Duque, E.Y.H. Chan, S. Chim, F.T.W. Ho, P.C. Tong, W.M. Lai, and M.H.L. Lee provided study-related clinical assessments and follow-up. D. Leung, S.M. Chan, S.T.K. Sze, J.H.Y. Lam, J.S. Rosa Duque, and Y.L. Lau collected clinical safety data. S.M.S. Cheng, L.C.H. Tsang, K.K.H. Kwan, and M. Peiris developed and performed S-RBD IgG and sVNT. X. Mu, Y. Chung, H.H.W. Wong, A.M.T. Lee, W.Y. Li, and W. Tu developed and performed the T cell assays. D. Leung, D.H.L. Lee, and J.H.Y. Lam curated, analyzed, and visualized the data. D. Leung, X. Mu, S.M.S. Cheng, J.S. Rosa Duque, D.H.L. Lee, J.H.Y. Lam, and S.M. Chan validated the data. D. Leung and E.Y.H. Chan drafted the manuscript and were supervised by A.L.T. Ma, J.S. Rosa Duque, and Y.L. Lau, with input from X. Mu, and S.M.S. Cheng. All authors reviewed and approved the final manuscript. We thank the staff at Community Vaccination Centers at Ap Lei Chau Sports Centre, Gleneagles Hospital Hong Kong, and Sun Yat-Sen Memorial Park Sports Centre, and the University of Hong Kong Health System. The investigators are grateful to all clinical research team members and laboratory staff of the Department of Pediatrics and Adolescent Medicine at the University of Hong Kong for their research support. We are most thankful to the study participants, as well as clinicians and laboratory staff who have provided clinical care and testing to the patients. FUNDING This study was supported by the research grants COVID19F02, COVID19F10, and COVID19F12 from the Hong Kong SAR Government, which was not involved in the study design, performance, interpretation, or publication of this project. DATA SHARING All requests to share the pseudonymized data underlying the conclusions of this paper from researchers will be facilitated by the authors, subject to ethics approval. Enquiries should be addressed to [email protected]. Download .pdf (2.33 MB) Help with pdf files