Study demonstrates increased effectiveness of third BNT162b2 dose against SARS-CoV-2 infection and hospitalization

By Colin Lightfoot, M.Sc. Infection and ImmunityReviewed by Benedette Cuffari, M.Sc.Dec 28 2021

In both clinical and real-world settings, the Pfizer-BioNTech BNT162b2 messenger ribonucleic acid (mRNA) vaccine has proven to be highly effective against the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. By June and July 2021, the SARS-CoV-2 Delta variant was the dominant circulating strain worldwide by June and July 2021. Soon after, reports of reduced effectiveness of BNT162b2 and other coronavirus disease 2019 (COVID-19) vaccinations against SARS-CoV-2 infections began to rise, raising concerns that infections with the Delta variant could further elude vaccine-induced protection.

Study: Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: a retrospective cohort study. Image Credit: KT Stock Photos / Shutterstock.com

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Recent studies have found that a reduction in BNT162b2 effectiveness over time is primarily attributed to fading immunity rather than the Delta variant escaping vaccination protection. As a result, a third (booster) dose of BNT162b2 has been recommended to restore initially high levels of protection and reduce the spread of SARS-CoV-2.

In a recent Lancet preprint* retrospective cohort study, researchers analyzed electronic health records from Kaiser Permanente Southern California between December 14, 2020, and December 5, 2021, to assess vaccine effectiveness (VE) of two and three doses of BNT162b2 against SARS-CoV-2 infections and COVID-19-related hospital admission. VE was calculated using hazards ratios from adjusted Cox models.

About the study

In the current study, VE against SARS-CoV-2 infection declined with increasing time since vaccination among those who had received only two doses of BNT162b2. More specifically, VE reduced from 85% within the first month following vaccination (to 49% after seven months. In particular, individuals aged 18-64 years and older, as well as immunocompromised and non-immunocompromized groups, showed a decline in VE when immunized with only two doses.

Overall adjusted VE estimates for COVID-19 hospital admissions among all adults who received only two doses were 90% at one month and 88% at seven months, thereby indicating no significant fading. VE decreased in immunocompromised patients from 93% after one month to 74% after seven months after receiving two doses of vaccine, although this data was not statistically significant.

Individuals who received three doses of BNT162b2 had an adjusted VE of 88% against SARS-CoV-2 infections and 97% against COVID-19-related hospital admissions after being immunized. The VE of the three-dose regiment against SARS-CoV-2 infection was similar across all age groups and immunocompromised status, ranging from 84% to 89%. VE against infections after three doses was higher in individuals 65 and older than VE in the first month after only two doses.

Estimates of three-dose VE against hospital admission were similar across age groups, which included a VE of 97% for 18 years and older, 65 years and older, and 75 years and older; however, VE was slightly lower for immunocompromised patients as compared to non-immunocompromised patients at 87% and 98%, respectively. VE against hospitalization with three doses was higher among all people as compared to VE one month after only two doses and 97% and 90%, respectively.

When comparing adults who received three doses of BNT1612b2 to those who received only two doses with at least six months between the second and third doses, the relative VE against infections and hospital admissions was 75% and 70%, respectively. In terms of the ability of the three-dose vaccine regiment to prevent hospital admission in the elderly, the relative VE of the third dosage against two doses was 83% in those 65 years and older and 86% in those 75 years and older.

Implications

The findings of the current study, along with improved immunogenicity, high efficacy, and tolerable safety profile of a third BNT162b2 dose observed in clinical trials and preliminary real-world data from the BNT162b2 booster program in Israel, support the benefit of broad age-based recommendations for the third dose. This is particularly true in the context of the Delta variant and the potential introduction of the highly transmissible Omicron variant.

Preliminary immunogenicity and real-world efficacy findings also suggest that third doses of BNT162b2 will likely aid in conferring Omicron protection. However, more research is needed to compare the real-world VE of two and three dosages of BNT162b2 to this novel variant.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources