Declining effectiveness of the BNT162b2 vaccine in adolescents infected with COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In May 2021, the United States Food and Drug Administration (FDA) and the European Medicines Agency approved the BioNTech/Pfizer mRNA BNT162b2 vaccine for adolescents. Subsequently, in June 2021, a vaccination campaign commenced for adolescents in Israel.

Study: Waning Effectiveness of the BNT162b2 Vaccine Against Infection in Adolescents. Image Credit: Irina Shatilova/Shutterstock

Background

Both clinical trials and real-time studies showed the short-term effectiveness of the BioNTech/Pfizer mRNA BNT162b2 vaccine for adolescents. However, not much evidence is available on the vaccine's long-term effectiveness in this age group. Many studies have indicated that BNT162b2 vaccine-induced immunity among adults declines within a few months of vaccination. However, studies have shown that the vaccinated population remained protected against severe COVID-19 disease for a relatively long period.

Scientists have indicated that it is important to understand how long a vaccinated adolescent remains protected against severe COVID-19 infection and the longevity of the vaccine-induced neutralizing immunity in this group. This would help healthcare policymakers to formulate strategies to protect this group.

Recently, the US FDA and Israel have extended the eligibility of COVID-19 booster vaccine for ages between twelve and fifteen years. Many other countries are still pondering over this decision.

To better understand the effectiveness, researchers have conducted a retrospective matched case-control study to determine the protection period conferred by the BNT162b2 vaccine on adolescents aged 12 to 16. This study has been published on the medRxiv* preprint server. 

A new study

In this study, the authors obtained data from the centralized computerized database of Maccabi Healthcare Services (MHS), which is Israel's second-largest Health Maintenance Organization comprising around 2.5 million members. Scientists revealed that the six-month follow-up period of this study, i.e., from June 15^th to December 8^th, 2021, is the longest follow-up period study published to date for this age group. In this study period, the Delta variant was the dominant circulating strain.

Researchers formulated a matched case-control design to evaluate the association between the time since BNT162b2 vaccination and the incidence of SARS-CoV-2 infections. Individuals between twelve and sixteen with COVID-19 infection, confirmed via PCR test, were assessed between June 15 and December 8, 2021. In this study, two outcomes, i.e., a documented SARS-CoV-2 infection (regardless of symptoms) and a symptomatic infection (COVID-19), were considered separately. The control group included adolescents who had no history of COVID-19 infection.

Main findings

The findings of this study are in line with previous research, which suggested that the BioNTech/Pfizer mRNA BNT162b2 vaccine provided robust short-term protection against any SARS-CoV-2 infection with the Delta variant in adolescents.

Scientists used matched case-control analysis to estimate a peak vaccine effectiveness between two weeks and three months following receipt of the second dose. They found 85% of vaccine effectiveness after two weeks of the administration of second dose vaccine and 90% effectiveness after three months against SARS-CoV-2 infection.

However, similar to that of adults, researchers observed waning of vaccine effectiveness in adolescents. This study reported that the long-term protection conferred by the vaccine was reduced to 75-78%, 3 to 5 months after the second dose. The levels of neutralizing antibodies decreased to 58% against infection and 65% against symptomatic infection after five months. 

Scientists stated that even without vaccination, adolescents are at a lower risk of hospitalization and death due to COVID-19 infection compared to adults. Hence, it is up to the healthcare policymakers to decide if the adolescents should be vaccinated or made eligible for the COVID-19 booster vaccine. This decision would be based on policy goals such as if the focus is to reduce transmission of SARS-CoV-2 in the population in the short term or to lower the burden of disease in the population.

Limitations

The authors highlighted some of the limitations of this study. Participants who were not tested for infection immediately after the administration of the first dose of the COVID-19 vaccine, as the symptoms might have been attributed to vaccines' side effects, were compared to the unvaccinated group who were tested immediately.

Hence, there is a marginal chance of short-lived biased results. Another limitation is the generalizability of results in the context of the emergence of novel SARS-CoV-2 variants. Researchers have only studied the vaccine effectiveness against the Delta variant that was the dominant strain in Israel at the time of this study. However, the efficacy of the vaccine against the present dominant strain, i.e., Omicron variant, has not been assessed.

Conclusion

This study revealed that compared to the unvaccinated group, adolescents who received two doses of the BNT162b2 vaccine were at a lower risk of contracting SARS-CoV-2 infection or symptomatic infection. However, similar to adults, vaccine-induced immune protection against SARS-CoV-2 infection declined with time, i.e., around three months after vaccination.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.