What is the impact of reduced doses of COVID-19 vaccine in young cohorts?

Recent studies published in Open Forum Infectious Diseases The journal evaluated the effect of lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses in the younger population.

Background

For most age groups, SARS-CoV-2 messenger ribonucleic acid RNA (mRNA) vaccination has been highly successful in protecting the 2019 CoV disease (COVID-19) from the pandemic. According to the latest data, the vaccine efficacy (VE) of the SARS-CoV-2 mRNA vaccine appears to be lower in children aged 5 to 11 years than in adults. In addition, understanding the reason for this phenomenon is essential to developing an appropriate vaccination approach for this population to move forward.

the study

In this study, we analyzed the VE of the COVID-19 mRNA vaccine and its associated mechanism in adolescents, children, and young adults. This is because the vaccine doses in these groups were lower than in adults.

Efficacy of COVID-19 mRNA vaccine in young adults, children, and adolescents

The VE of the SARS-CoV-2 BNT162b2 vaccine for COVID-19 years 5 to 11 years was 91% during the 2-month monitoring period in clinical trials prior to the emergence of the Omicron variant in the United States (US). ). After the vaccine was approved on October 29, 2021, the children were fully vaccinated by December 13, 2021, just in time for the introduction of Omicron.

However, according to preliminary information from the New York State Department of Health, the VE of children aged 5 to 11 years decreased from 68% to 12% between December 13, 2021 compared to January 24, 2022. , The hospitalization rate has decreased from 100% to 48%. On the other hand, VE between the ages of 12 and 17 decreased from 66% to 51% for infectious diseases and from 85% to 73% for hospitalization.

During the study period, Omicron infections in New York increased from 19% on December 13, 2021 to over 99% on January 24, 2022. The median time after vaccination was 51 days for children aged 5-11 years and 211 days for children aged 5-11 years. 12 to 17.

Removing the entanglement of post-vaccination time from testing of recently vaccinated children in New York, the incidence of infection ratio is 1.1, 12- for children 5-11 years 28-34 days after immunization. I was 2.3 at the age of 17. When the analysis was limited to the Omicron period, information from the US Centers for Disease Control and Prevention (CDC) showed slight variation with age, with VE for children aged 5-11 years being 51%, but 45% and 34. It was% t. Children aged 12 to 15 and 16 to 17, respectively.

However, during periods of predominance of pooled Delta and Omicrons, double-dose VE for COVID-19-related hospitalizations of 5-11, 12-15, and 16-17 years continued at 73-94%. did. The available results show that BNT162b2 is less effective in young children, but further research is needed to support these findings.

Mechanism of reduced vaccine efficacy in younger age groups

According to one theory, low doses of 10 µg BNT162b2 given at 3-week intervals contributed to the reduced efficacy of children aged 5 to 11 years. however, Neutralizing antibody This suggests that this was not the case. Evidence presented at the Vaccine and Related Biological Products Advisory Board on October 26, 2021. Advisory Committee on Immunization Implementation (ACIP) meeting on November 2, 2021. A meeting between the Food and Drug Administration (FDA) and the CDC Advisory Board states that adolescents, children and young adults may achieve optimal humoral responses at existing BNT162b2 vaccine doses.

When 30 µg of BNT162b2 is administered twice at 21-day intervals, the geometric mean 50% neutralization titer of SARS-CoV-2 is 1146.5, respectively, in individuals aged 16 to 25 and 12 to 15 years after the second month. And became 1239.5. shot. After two doses of 10 µg at 3-week intervals, approximately the same titer of 1197.6 was achieved in children aged 5-11 years.

Children aged 9-11, 7-8, and 5-6, further analyzed by age subgroup, gained approximately the same titers of 1191.5, 1236.1, and 1164.1. These titers were more than three times higher than the peak titers achieved by adults 7 days after the second dose, indicating that children and young adults show a significant humoral immune response. The results suggested that even doses less than 10 µg could produce significant levels of neutralizing antibodies in children aged 5 to 11 years.

At current doses, adolescents, children, and young adults produce significantly higher titers than adults, so other causes of decreased VE should be considered.Omicron variants decrease Effectiveness of COVID-19 vaccination in all populations is most likely to explain most of the reduced efficacy of children aged 5-11 years. Other possible explanations include a short time in the young cohort from vaccination to infection, changes in circulating viral strains between age cohorts, past SARS-CoV-2 exposure, and unconfirmed low efficacy of the mRNA vaccine in the young population. Gender is included.

After vaccination, T and B cell responses continue to develop for months, similar to immunity to severe illness. Therefore, children aged 12 to 17 years in New York have 211 days, whereas children aged 5 to 11 years are less effective against hospitalization seen in younger samples during the 51-day post-vaccination period. It may be due.

In addition, given the dramatic increase in Omicron outbreaks during the study period, it is possible that there was variability in the variants prevalent in high school, primary school and junior high school. Moreover, there was an important SARS-CoV-2 seroprevalence in the United States. Prior to the increase in delta mutations, the age group 5 to 11 had the highest seroprevalence of 42% in June 2021. Previous SARS-CoV-2 exposure was associated with a reduced risk of catastrophic consequences, but it was unclear how this altered the immune response of the population.

Approach to strengthen VE in younger age group

The team has shown that mRNA vaccination is a new vaccination approach that elicits both T and B cell responses and has the potential to produce superior vaccines against some of the pathogens currently under development. Said. Nevertheless, the first trial of the double-dose BNT162b2 series found that this approach was ineffective in children aged 2-5 years. Therefore, the experiment was modified to evaluate a triple dose series.

Factors such as previous seasonal CoV exposure may be involved in the significantly altered immune response seen in the elderly, which was not present in younger children who were less or not exposed to CoV at all. .. Maximizing CoV vaccination in children relies on understanding the mechanisms that cause the reduced efficacy of BNT162b2 in children.

Changing the dosing interval was one action to increase the immunogenicity of individuals aged 12 to 39 years. New studies show that widening the first and second doses of the mRNA vaccine increases immunogenicity while reducing side effects.

On February 4, 2022, ACIP reviewed new information on extended dosing intervals, and an 8-week gap could be ideal for some individuals over 12 years of age, especially men aged 12-39 years. I have issued a recommendation that there is sex. The clinical trial of BNT162b2 has been extended to include a formal evaluation of a lower 10 µg dose given twice at 8-week intervals in patients aged 12-18 years and older. The team emphasized the need for studies examining longer dosing gaps in children under 12 years of age to see if this tactic can enhance the immunogenicity and efficacy of mRNA vaccines in younger populations. did.

Side effects of current mRNA vaccine doses in young cohorts

Current doses of mRNA vaccines also face higher side effects in addition to reduced efficacy in adolescents, children, and young adults. The cause of COVID-19 vaccine-related myocarditis was unknown. However, the prevalence of this rare event is lower than mRNA-1273 (100 µg per dose) after vaccination with BNT162b2 (30 µg per dose), and myocarditis may be dose-related. It supports the idea that there is.

COVID-19 vaccine-related myocarditis also occurred frequently after the second vaccination, especially at dosing intervals of 4 weeks or less. However, increasing the time of the first and second doses to 8 weeks reduced the frequency of myocarditis.

At the FDA Brief on October 26, 2021, there was a meeting that COVID-19 vaccine-related myocarditis was probably dose- and dose-related. Nevertheless, the reduction in the incidence of myocarditis after the third or booster shot compared to the reduction in the incidence with extended dosing intervals, the interval interval, not the dose number, minimizes myocarditis. It means that it may be a restraining strategy.

Conclusion

Studies have shown that SARS-CoV-2 mRNA vaccination is less effective in children aged 5 to 11 years. Neutralizing antibody titers induced by the COVID-19 vaccine in adolescents, children, and young adults showed that low doses were not the cause of the low VE in these cohorts.

To optimize the COVID-19 vaccination approach for younger populations in the future, determine if mRNA vaccination technology is less effective in the young cohort, and dosing, dosing gaps for adolescents, children, and young adults. , And whether the dose frequency needs to be adjusted.