A recent study published within the Open Forum Infectious Diseases journal evaluated the impact of the lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine dosages in younger populations.

Study: Coronavirus Disease 2019 Vaccine Dosage in Children, Adolescents, and Young Adults: Is Less More? Image Credit: Ira Lichi/Shutterstock

Background

In most age groups, the SARS-CoV-2 messenger ribonucleic acid RNA (mRNA) vaccinations were significantly successful in protecting against the CoV disease 2019 (COVID-19) pandemic. In response to probably the most recent data, vaccine efficacy (VE) of SARS-CoV-2 mRNA vaccines appears to be lower in children aged five to 11 than in adults. Besides, understanding the explanation for this phenomenon is crucial for creating appropriate vaccination approaches for this population moving forward.

The study

The current work analyzed the VE of COVID-19 mRNA vaccines and the associated mechanisms in adolescents, children, and young adults, given the vaccine doses were lower in these groups in comparison with adults.

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

VE of the SARS-CoV-2 BNT162b2 vaccine in five- to 11-year-olds against COVID-19 was 91% through the two-month monitoring period in a clinical experiment before the emergence of the Omicron variant in the US (US). Following the vaccine’s approval on October 29, 2021, children were fully vaccinated by December 13, 2021, just in time with the introduction of Omicron.

Nonetheless, based on preliminary information from the Recent York State Department of Health, VE in children aged 5 to 11 decreased from 68 to 12%, and hospitalization rates from 100 to 48% during December 13, 2021, in comparison with January 24, 2022. Alternatively, VE in those aged 12 to 17 dropped from 66 to 51% for infections and from 85 to 73% for hospitalization.

In the course of the study period, Omicron infections in Recent York increased from 19% on December 13, 2021, to above 99% on January 24, 2022. The median period following vaccination was 51 days for kids aged 5 to 11 and 211 days for those aged 12 to 17.

When removing the confounding effect of time after vaccination from an examination of recently vaccinated children from Recent York, the incidence rate ratio for infection was 1.1 for those aged five to 11 and a couple of.3 for 12 to 17 years at 28 to 34 days after immunization. When the evaluation was limited to the Omicron period, information from the Centers for Disease Control and Prevention (CDC) demonstrated slight variation by age, with a VE of 51% in children aged 5 to 11, in comparison with 45% and 34%t in children aged 12 to fifteen and 16 to 17, respectively.

Nonetheless, through the pooled Delta- and Omicron-predominant timeframes, two-dose VE towards COVID-19-linked hospitalization for five–11, 12–15, and 16–17 years continued at 73 to 94%. The available results indicate that BNT162b2 was less effective in younger children, yet further research is required to corroborate these findings.

Mechanisms of reduced vaccine efficacy in younger age groups

One theory holds that the lower dosage of 10 µg of BNT162b2 delivered three weeks apart was the reason behind the poor efficacy in children aged 5 to 11; nevertheless, evidence on neutralizing antibodies suggests that this was not the case. The evidence presented on the Vaccines and Related Biological Products Advisory Committee meeting on October 26, 2021; Advisory Committee on Immunization Practices (ACIP) meeting on November 2, 2021; and Food and Drug Administration (FDA) and CDC Advisory Committee meetings posit that adolescents, children, and young adults might attain an optimum humoral response with the prevailing BNT162b2 vaccine doses.

Two 30-µg BNT162b2 doses administered in a 21-day interval resulted in geometric mean 50% neutralization titers of SARS-CoV-2 of 1146.5 and 1239.5 in individuals aged 16 to 25 and 12 to fifteen years, respectively, one month after the second shot. Almost equivalent titers, 1197.6, were attained in children aged 5 to 11 years after two 10-µg doses administered three weeks apart.

Children aged September 11, 7-8, and 5-6 years acquired almost equivalent titers of 1191.5, 1236.1, and 1164.1 when further analyzed by age subgroup. These titers show that children and young adults have significant humoral immune reactions because they were greater than three times higher than the height titers attained by adults seven days following the second dose. Consequently, it was conceivable that doses below 10 µg could still produce significant levels of neutralizing antibodies in five to 11-year-old children. 

Other causes for the decreased VE have to be considered because, with the present dose, adolescents, children, and young adults produce noticeably high titers than adults. The Omicron variant reduces the efficacy of the COVID-19 vaccinations in all populations, which more than likely explains a big portion of the decreased efficacy amongst children aged 5 to 11 years. Other possible explanations include the younger cohort’s shorter time between vaccination and infection, variations in circulating viral strains amongst age cohorts, past SARS-CoV-2 exposure, and unidentified lower effectiveness of mRNA vaccines amongst younger populations. 

After vaccination, T- and B-cell responses proceed to develop for several months, as does immunity against severe illness. Subsequently, the 51-day post-vaccination period for kids aged 5 to 11 in comparison with 211 days for kids aged 12 to 17 in Recent York might have attributed to the lower efficacy against hospitalization seen within the younger sample.

Moreover, given the dramatic rise in Omicron occurrence over the study period, there might need been variations within the variants circulating in high, elementary, and middle schools. Besides, there was a major SARS-CoV-2 seroprevalence within the US. Before the Delta variant increase, the age group of 5 to 11 had the best seroprevalence in June 2021 at 42%. Previous SARS-CoV-2 exposure was linked to a decreased risk of catastrophic outcomes, but it surely was unclear how this will likely have modified the population’s immune reactions.

Approaches to reinforce VE in younger age groups

The team noted that mRNA vaccination was a novel vaccination approach that induces each T- and B-cell responses and shows promise for producing superior vaccines against quite a few pathogens, a few of which at the moment are under development. Yet, an initial trial of the two-dose BNT162b2 series found the approach was ineffective in children aged two to 5. Thus, the experiment was modified to evaluate a three-dose series. 

Aspects like prior seasonal CoV exposure might need a component within the notably altered immunological response seen in older those that weren’t present in younger children not exposed to CoVs as much or in any respect. Maximizing CoV vaccination in children is determined by understanding the mechanism causing BNT162b2’s decreased efficacy in children.

Altering the dose intervals was one motion tried to reinforce immunogenicity in individuals between the ages of 12 and 39. Recent research has shown that spreading out the initial and second doses of mRNA vaccines increases immunogenicity while reducing opposed reactions.

On February 4, 2022, the ACIP reviewed the brand new information regarding prolonged dose intervals and published a suggestion that an eight-week gap might be ideal for some individuals aged 12 and older, particularly for males between the ages of 12 to 39. The continued clinical trial for BNT162b2 has been expanded to incorporate formal evaluation of the lower 10-µg dose, administered in two doses eight weeks apart for patients aged 12 to 18 and older. The team highlighted the necessity for studies examining longer dosing gaps in children under 12 years to see if this tactic can increase the immunogenicity and effectiveness of mRNA vaccines in younger populations.

Uncomfortable side effects of present mRNA vaccines doses in younger cohorts

With the current dose of the mRNA vaccines, adolescents, children, and young adults also face higher unintended effects along with reduced efficacy. The reason behind COVID-19 vaccine-associated myocarditis was unknown. Nonetheless, the prevalence of this unusual event was lower after vaccination with BNT162b2 (30 µg per dose) than mRNA-1273 (100 µg per dose), reinforcing the concept that the myocarditis could also be dose-related.

COVID-19 vaccine-related myocarditis was also more frequent after the second shot, especially with dosing intervals of ≤ 4 weeks. Nonetheless, increasing the time between the primary and second doses to eight weeks reduced the frequency of myocarditis. 

The FDA Temporary for October 26, 2021, meeting noted that COVID-19 vaccine-linked myocarditis was probably related to dose number and dosage. Nevertheless, the decreased myocarditis incidence after the third or booster shot relative to the reduced incidence with prolonged dosing intervals, implies that interval spacing, as an alternative of dose number, may be the strategy to attenuate myocarditis.

Conclusions

In response to the study findings, the SARS-CoV-2 mRNA vaccinations demonstrated reduced efficacy in children aged 5 to 11. Neutralizing antibody titers induced by the COVID-19 vaccines in adolescents, children, and young adults illustrated that lower dosage was not liable for the lower VE in these cohorts.

Optimizing COVID-19 vaccination approaches for younger populations in the long run requires determining whether mRNA vaccination techniques were less effective in younger cohorts and identifying if adolescents, children, and young adults need adjusting the dosage, dosing gaps, and the variety of doses.