Pfizer and BioNTech Announce Positive Phase 1 Data for BNT162b2 mRNA COVID-19 Vaccine Candidate

Compiled by Keke

Last month, BioNTech and Pfizer released positive data from the Phase I/II clinical trial of their jointly developed mRNA COVID-19 vaccine candidate BNT162b1 in Germany, and announced that they had reached a $1.95 billion agreement with the U.S. government for BNT162. (Related reading:$1.95 Billion! Pfizer/BioNTech COVID-19 Vaccine Secures Major Order from U.S. Government）

Recently, the two companies announced safety and immunogenicity data from a Phase 1 clinical study within their BNT162 mRNA-based vaccine program. The results showed that seven days after the second dose of the experimental vaccine BNT162b2 (30 μg), the geometric mean titers (GMTs) of SARS-CoV-2 neutralizing antibodies in younger and middle-aged adults (18–55 years) were 3.8 times higher than those in patients who had recovered from COVID-19, while the GMTs in older adults (65–85 years) were 1.6 times higher than those in recovered patients. These findings indicate that the BNT162b2 vaccine induces higher average concentrations of anti-SARS-CoV-2 antibodies and demonstrates robust immunogenicity in both younger and older populations.

It is reported that the study compared the efficacy of the two-dose regimens of the experimental mRNA vaccines BNT162b1 and BNT162b2. In participants, BNT162b1 and BNT162b2 induced similar dose-dependent geometric mean titers (GMTs) of SARS-CoV-2 neutralizing antibodies. Following the second dose, GMTs in participants increased significantly, demonstrating the clear benefit of the two-dose vaccination regimen.

However, in terms of safety, systemic events following BNT162b2 vaccination were milder than those following BNT162b1. The BNT162b2 vaccine was well tolerated across all populations, with fewer than 20% of participants experiencing mild to moderate fever. Severe systemic events (including fatigue, headache, chills, myalgia, and arthralgia) occurred only in a small subset of younger participants and were transient and manageable. The two companies have advanced the two-dose regimen of the 30 μg BNT162b2 vaccine into Phase 2/3 clinical trials, which are expected to enroll 30,000 participants in the United States, Argentina, and Brazil.

BioNTech is currently still evaluating the T-cell immune response induced by BNT162b2. Previously, the two companies announced that participants vaccinated with BNT162b2 exhibited a more broadly recognized specific T-cell response against the SARS-CoV-2 spike antigen compared to those receiving the BNT162b1 candidate vaccine. Moreover, BNT162b2 was shown to simultaneously induce robust CD4+ and CD8+ T-cell responses targeting both the receptor-binding domain (RBD) and the remaining spike glycoprotein regions not included in the BNT162b1 vaccine candidate.

BNT162b2 is an mRNA vaccine encoding an optimized full-length SARS-CoV-2 spike glycoprotein. Selected in late July this year, it entered late-stage clinical trials within just one month. Pfizer and BioNTech have planned to seek regulatory approval for the vaccine as early as October, with a goal of supplying 100 million doses globally by the end of this year and delivering 1.3 billion doses by the end of 2021. Other vaccines under rapid development include Moderna’s mRNA-1273, AstraZeneca’s AZD1222, and Johnson & Johnson’s Ad26.COV2.S.

Furthermore, it remains to be seen whether any COVID-19 vaccine candidate can provide long-term protection such that annual vaccination is sufficient to prevent viral infection. Currently, Phase I clinical data focus solely on the production of neutralizing antibodies or the stimulation of human T cells by the vaccine; these measures may not necessarily translate into genuine protective efficacy. Clearly, the metric that researchers should prioritize in Phase III trials is the vaccine’s real-world effectiveness in preventing infection.

The global COVID-19 pandemic has indeed ushered in a new paradigm for vaccine development. In addition to the key frontrunners mentioned above, early-stage trials of more vaccines are rapidly underway (see figure below). Among these, the most closely watched is CureVac’s candidate vaccine, CVnCoV, which has quickly advanced to Phase 2 clinical studies, although Phase 1 clinical data will not be available until the fourth quarter of this year. The company announced last week that it had held preliminary discussions on supplying up to 405 million doses to the European Union.

Furthermore, the adenovirus vaccine Gam-COVID-Vac, developed by Russia’s Gamaleya Research Institute using an “unconventional” approach, has also drawn significant attention. It is reported that the vaccine has completed Phase II clinical trials; however, no relevant human data have been released to date. Moreover, the vaccine received marketing approval from Russian drug regulatory authorities this month, despite the absence of Phase III clinical trial results and longer-term efficacy data.

Reference Sources:

1、Pfizer, Germany’s BioNTech release new data on Covid-19 vaccine

2、The next triggers in Covid-19 vaccine development