Recent research from Singapore questions whether two doses of COVID-19 vaccine are sufficient for children, exploring the necessity of booster shots amid variant concerns.
Since the start of the COVID-19 pandemic, extensive research in epidemiology, clinical practice, virology and the COVID-19 vaccine has greatly increased our understanding of the virus and its impact on human health.
Introduction: The Dynamics of Paediatric COVID-19
Initially, children were less severely affected than adults, had milder or negligible symptoms, and represented a smaller fraction of cases. However, as the virus evolved and the emergence of more transmissible variants like Delta and Omicron, children’s susceptibility became more apparent. To mitigate these challenges, studies demonstrated the safety and efficacy of the vaccines on children, showing that the benefits outweigh the risks. Recognising these benefits, governments worldwide then implemented vaccination programs for children aimed to address the direct impacts of the virus and severe outcomes such as Multisystem Inflammatory Syndrome in Children (MIS-C) and long-COVID. This article explores the recent findings from a Singapore study suggesting that two vaccine doses in children may be sufficient. By examining these insights, healthcare professionals can better understand the current research and ensure their advice aligns with the latest scientific evidence and evolving global and governmental health policies.
Overview of the Singapore Study
In a newly published study in Nature Medicine, researchers from the NUS Yong Loo Lin School of Medicine (NUS Medicine) and Duke-NUS Medical School investigated the minimum threshold of immune response and the number of mRNA vaccination doses required to protect against COVID-19 in children aged 5 to 12 years old. All 110 participants received two doses of 10mcg Pfizer/BioNTech mRNA COVID-19 vaccination. Amongst the participants, a proportion received an additional booster dose five months following their second dose. The study also monitored instances of whether the children were naturally infected with COVID-19 subsequently. Over a year, the researchers assessed their immune response by measuring antibodies, memory B cells, and T cells.
Key Findings on Immunity and Vaccination
These are the key results from the study:
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Superior Hybrid Immunity Post-Vaccination
After two doses of vaccination (hybrid immunity), children who were infected showed the highest neutralising antibodies and T-cell responses. A third vaccine dose alone is insufficient to achieve these antibody levels.
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Longevity of Immune Responses
The subset of children who remained infection-free showed sustained antibody, memory B cell, and T cell responses over a year. A booster dose increased antibody titers but did not affect memory B or T cell responses.
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T Cells as a Protective Factor
T-cell responses are the most important factor in protecting against symptomatic infection before hybrid immunity. T-cells are also effective against variants like Omicron. Antibody titers only correlate with protection after hybrid immunity.
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The Onion Model
The researchers introduced a multi-layered immune system defence model, highlighting the importance of T-cell responses in assessing COVID-19 protection and moving beyond antibodies.
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Side Effects and Asymptomatic Infections
The booster dose led to more side effects, like fever, fatigue, and pain, than the first two doses. Asymptomatic infections were identified using serology and T-cell responses, highlighting the importance of both criteria for detection.
Implications for Healthcare Professionals
Despite the promising results suggesting that two doses of the vaccine may be sufficient for long-lasting immunity, healthcare professionals should still remain cautious. This study, involving 110 participants in a single country, may not capture broader, more diverse population dynamics. Furthermore, guidelines and recommendations can vary significantly between different countries, so it is important to adhere to them.
Considering Local Regulations
In advising patients, healthcare professionals should consider local regulations and the latest research. For instance, the Singapore government, its Ministry of Health and Singapore’s Expert Committee on Immunisation have taken the stance that additional booster doses for children should still be encouraged. While the study presents a compelling case for minimal additional benefits from a third dose in children, other international studies, including those from the United States, show enhanced protection with a booster- among 5 to 11-year-olds, there was an increase from 20 to 55% protection against infection during the Omicron variant period.
Antibodies: First Line of Defence
While T-cells play a crucial role in a deeper level of immune defence and for the long-term protection against COVID-19, antibodies still act as the initial barrier against infection. Antibodies are the first line of defence to act quickly in neutralising the virus and preventing it from entering cells. A study on booster shots of CoronaVac showed that the booster is well-tolerated and resulted in a significant increase in neutralising antibody levels against both the original virus and the Omicron variant, with seropositivity rates reaching 100% against the original and over 90% against the Omicron variant.
Conclusion: Navigating the Complex Landscape of Paediatric COVID-19 Vaccination
As the situation evolves, it is crucial for healthcare professionals to stay informed about the latest research and tailor their advice based on comprehensive data, including the prevalence of variants and local health policies. The Singapore study from NUS Yong Loo Lin School of Medicine and Duke-NUS Medical School suggests that two doses of the Pfizer/BioNTech vaccine may suffice for long-term immunity in children aged 5 to 12, emphasising the importance of T cells and hybrid immunity. However, several global studies indicate variable efficacy of booster doses and improving protection in some. Healthcare professionals should advocate for adherence to updated vaccination schedules that may include booster doses for children, guided by ongoing research and regulatory approvals. This balanced approach will ensure that children receive the most effective and maximal protection against COVID-19, addressing both short-term risks and long-term health implications.
References
- Sadeghi, S., Kalantari, Y., Shokri, S., Fallahpour, M., Nafissi, N., Goodarzi, A., & Valizadeh, R. (2022). Immunologic response, efficacy, and safety of vaccines against COVID-19 infection in healthy and immunosuppressed children and adolescents aged 2 – 21 years old: A systematic review and meta-analysis. Journal of Clinical Virology, 153, 105196. https://doi.org/10.1016/j.jcv.2022.105196
- Nathanielsz, J., Toh, Z.Q., Do, L.A.H., et al. (2023). SARS-CoV-2 infection in children and implications for vaccination. Pediatric Research, 93, 1177–1187. https://doi.org/10.1038/s41390-022-02254-x
- Zhong, Y., Kang, A.Y.H., Tay, C.J.X., et al. (2024). Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children. Nature Medicine. https://doi.org/10.1038/s41591-024-02962-3
- Tan, J. (2024, April 30). COVID-19 booster dose encouraged for kids, says MOH after NUS study shows 3rd jab not needed. Straits Times. https://www.straitstimes.com/singapore/covid-19-booster-dose-encouraged-for-kids-says-moh-after-nus-study-shows-3rd-jab-not-needed
- Wang, L., Wu, Z., Ying, Z., et al. (2022). Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents. Nature Communications, 13, 6952. https://doi.org/10.1038/s41467-022-34280-y
- Klein, N.P., Stockwell, M.S., Demarco, M., et al. (2022). Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA vaccination in preventing COVID-19-associated emergency department and urgent care encounters and hospitalizations among nonimmunocompromised children and adolescents aged 5-17 years – VISION Network, 10 states, April 2021-January 2022. MMWR Morbidity and Mortality Weekly Report, 71(9), 352-358. https://doi.org/10.15585/mmwr.mm7109e3
