Immunogenicity and reactogenicity of fractional heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5�-year-old Thai children A multicenter prospective double-blind randomized control trial
Immunogenicity and reactogenicity of fractional heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5�-year-old Thai children A multicenter prospective double-blind randomized control trial
Author
Wittawatmongkol O. Bunjoungmanee P. Kosalaraksa P. Laoprasopwattana K. Boonsathorn S. Chantasrisawad N. Sudjaritruk T. Niyomnaitham S. Senawong S. Srisutthisamphan K. Quan Toh Z. Rungmaitree S. Nanthapisal S. Phanthanawiboon S. Khantee P. Techasaensiri C. Hirankarn N. Pangprasertkul S. Chokephaibulkit K.
Affiliations
Department of Pediatrics Faculty of Medicine Siriraj Hospital Mahidol University Bangkok 10700 Thailand; Department of Pediatrics Faculty of Medicine Thammasat University Pathum Thani 12120 Thailand; Clinical Research Center Faculty of Medicine Thammasat University Pathum Thani 12120 Thailand; Department of Pediatrics Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand; Department of Pediatrics Faculty of Medicine Prince of Songkla University Songkhla 90110 Thailand; Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok 10400 Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines Faculty of Medicine Chulalongkorn University Bangkok 10330 Thailand; Department of Pediatrics Faculty of Medicine Chiang Mai University Chiang Mai 50200 Thailand; 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; Department of Immunology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok 10700 Thailand; 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; Department of Pediatrics The University of Melbourne Parkville VIC 3010 Australia; Infection and Immunity Murdoch Children's Research Institute Parkville VIC 3052 Australia; Research Unit in Infectious and Immunology Faculty of Medicine Thammasat University Pathum Thani 12120 Thailand; Department of Microbiology Faculty of Medicine Khon Kaen University Khon Kaen 40002 Thailand; Department of Microbiology Faculty of Medicine Chulalongkorn University Bangkok 10330 Thailand
Type
Article
Source Title
Vaccine
ISSN
0264410X
Year
2023
Volume
41
Issue
40
Page
5834-5840
Open Access
All Open Access Hybrid Gold
Publisher
Elsevier Ltd
DOI
10.1016/j.vaccine.2023.08.021
Abstract
Objective: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5�-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-?g) or half-dose (5-?g) BNT162b2 vaccines as follows: CoronaVac/10-?g-BNT162b2 (Group 1) CoronaVac/5-?g-BNT162b2 (Group 2) 10-?g-BNT162b2/10-?g-BNT162b2 (Group 3) or 10-?g-BNT162b2/5-?g-BNT162b2 (Group 4). A subset of participants from each arm received 10-?g-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�.51-folds higher than the second vaccination against BA.1. AEs were similar across arms all mild or moderate and fully resolved 2�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. ? 2023 The Authors
