PMID- 37586956 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20230911 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 41 IP - 40 DP - 2023 Sep 15 TI - Immunogenicity and reactogenicity of fractional, heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5-11-year-old Thai children: A multicenter, prospective, double-blind, randomized control trial. PG - 5834-5840 LID - S0264-410X(23)00953-2 [pii] LID - 10.1016/j.vaccine.2023.08.021 [doi] AB - OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-mug) or half-dose (5-mug) BNT162b2 vaccines as follows: CoronaVac/10-mug-BNT162b2 (Group 1), CoronaVac/5-mug-BNT162b2 (Group 2), 10-mug-BNT162b2/10-mug-BNT162b2 (Group 3), or 10-mug-BNT162b2/5-mug-BNT162b2 (Group 4). A subset of participants from each arm received 10-mug-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Wittawatmongkol, Orasri AU - Wittawatmongkol O AD - Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Bunjoungmanee, Pornumpa AU - Bunjoungmanee P AD - Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Clinical Research Center, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Kosalaraksa, Pope AU - Kosalaraksa P AD - Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Laoprasopwattana, Kamolwish AU - Laoprasopwattana K AD - Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand. FAU - Boonsathorn, Sophida AU - Boonsathorn S AD - Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. FAU - Chantasrisawad, Napaporn AU - Chantasrisawad N AD - Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. FAU - Sudjaritruk, Tavitiya AU - Sudjaritruk T AD - Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. FAU - Niyomnaitham, Suvimol AU - Niyomnaitham S AD - Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Siriraj Institute of Clinical Research (SICRES), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Senawong, Sansnee AU - Senawong S AD - Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Srisutthisamphan, Kanjana AU - Srisutthisamphan K AD - Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand. FAU - Quan Toh, Zheng AU - Quan Toh Z AD - Department of Pediatrics, The University of Melbourne, Parkville, Victoria 3010, Australia; Infection and Immunity, Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia. FAU - Rungmaitree, Supattra AU - Rungmaitree S AD - Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Nanthapisal, Sira AU - Nanthapisal S AD - Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Clinical Research Center, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand; Research Unit in Infectious and Immunology, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Phanthanawiboon, Supranee AU - Phanthanawiboon S AD - Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Khantee, Puttichart AU - Khantee P AD - Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand. FAU - Techasaensiri, Chonnamet AU - Techasaensiri C AD - Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. FAU - Hirankarn, Nattiya AU - Hirankarn N AD - Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. FAU - Pangprasertkul, Sipang AU - Pangprasertkul S AD - Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. FAU - Chokephaibulkit, Kulkanya AU - Chokephaibulkit K AD - Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Siriraj Institute of Clinical Research (SICRES), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: kulkanya.cho@mahidol.ac.th. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230814 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Neutralizing) RN - 0 (BNT162 Vaccine) RN - 0 (COVID-19 Vaccines) RN - 0 (sinovac COVID-19 vaccine) RN - COVID-19 vaccine booster shot SB - IM MH - Child MH - Child, Preschool MH - Female MH - Humans MH - Male MH - Antibodies, Neutralizing MH - BNT162 Vaccine MH - *COVID-19/prevention & control MH - *COVID-19 Vaccines/adverse effects MH - Prospective Studies MH - SARS-CoV-2 MH - Southeast Asian People MH - Vaccination MH - *Immunogenicity, Vaccine OTO - NOTNLM OT - COVID-19 vaccines OT - Fractional dosing OT - Heterologous regimens OT - Homologous regimens OT - Paediatric boosters OT - Paediatric vaccination COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/17 00:42 MHDA- 2023/09/11 06:43 CRDT- 2023/08/16 21:59 PHST- 2023/05/11 00:00 [received] PHST- 2023/07/17 00:00 [revised] PHST- 2023/08/08 00:00 [accepted] PHST- 2023/09/11 06:43 [medline] PHST- 2023/08/17 00:42 [pubmed] PHST- 2023/08/16 21:59 [entrez] AID - S0264-410X(23)00953-2 [pii] AID - 10.1016/j.vaccine.2023.08.021 [doi] PST - ppublish SO - Vaccine. 2023 Sep 15;41(40):5834-5840. doi: 10.1016/j.vaccine.2023.08.021. Epub 2023 Aug 14.