Pfizer and BioNTech Report Positive Phase 1/2 Results for mRNA-Based COVID-19 Vaccine Candidate BNT162b1 with Neutralizing Antibody Levels Exceeding Those in Recovered Patients

Pfizer and BioNTech Announce Positive Results from Phase 1/2 Clinical Trial of Their Jointly Developed mRNA-Based COVID-19 VaccinePfizer and BioNTech have announced that their jointly developed mRNA-based COVID-19 vaccine has yielded positive results in Phase 1/2 clinical trials. Following two doses, volunteers who received the 10 µg and 30 µg dosages exhibited SARS-CoV-2 neutralizing antibody titers reaching 1.8 and 2.8 times the levels observed in the serum of recovered patients, respectively. These preliminary clinical trial results have also been published on the preprint server medRxiv.

BNT162b1, an mRNA vaccine, is one of four mRNA vaccines currently under evaluation in clinical trials by the two companies. Pfizer and BioNTech plan to select the most promising candidate from these four vaccines for a large-scale, global Phase 2b/3 clinical trial, which could commence as early as this month. BioNTech has also entered into a collaboration agreement with Fosun Pharma for the clinical development and commercialization of these vaccines in China.

One of the key tools for overcoming the COVID-19 pandemic is a safe and effective vaccine. According to statistics from the World Health Organization, the candidate vaccine jointly developed by BioNTech and Pfizer is one of the 17 vaccine development projects currently in clinical trials worldwide. The two companies collectively selected four candidate vaccines for clinical testing. These candidates target either the full-length spike protein of SARS-CoV-2 or the receptor-binding domain (RBD) within the spike protein that binds to cellular receptors. BNT162b1 is an mRNA vaccine targeting the RBD of the spike protein. It encodes a trimeric RBD folded in its native conformation.

▲Different variants of the BNT162 coronavirus vaccine (Image source: Reference [2])

This Phase 1/2 clinical trial was conducted simultaneously in the United States and Europe, with healthy volunteers aged 18 to 55 years receiving different doses of the candidate vaccine. Some participants received two vaccine doses administered 21 days apart, while others received only a single dose.

Data obtained from the initial 45 vaccinated volunteers indicated that those who received two vaccine doses 21 days apart elicited a robust immune response. On day 7 after the second vaccination, IgG antibody levels binding to the receptor-binding domain (RBD) in the blood of volunteers who received 10 µg and 30 µg doses peaked, with geometric mean concentrations (GMCs) of 4,813 units/mL and 27,872 units/mL, respectively. These values were 8-fold and 46.3-fold higher than the average antibody levels observed in 38 serum samples collected from patients who had recovered from COVID-19.

Evaluation of neutralizing antibody titers against SARS-CoV-2 showed that the geometric mean titer (GMT) of neutralizing antibodies reached 168 and 267 in volunteers who received vaccine doses of 10 µg and 30 µg, respectively. These values were 1.8 and 2.8 times higher than the neutralizing antibody titers observed in sera from convalescent individuals.

▲Interim immunogenicity data for BNT162b1 (Image source: Reference [2])

In terms of safety, adverse events mainly included pain at the injection site and fever. The incidence of adverse events in volunteers who received 10 µg and 30 µg doses of the vaccine showed a dose-dependent relationship, with most being temporary mild to moderate reactions. After receiving the second vaccine dose, 8.3% of volunteers who received the 10 µg dose and 75.0% of those who received the 30 µg dose experienced fever exceeding 38°C. No serious adverse reactions occurred during the trial.

▲Interim Data on the Safety and Tolerability of BNT162b1 (Image source: Reference [1])

BioNTech and Pfizer will continue to monitor these volunteers for at least six months to assess the safety and immune response of the vaccine, including T-cell responses elicited by the vaccine. CD4+ and CD8+ T cells also play a crucial role in viral clearance. As it is currently not possible to predict the protective efficacy of candidate vaccines against SARS-CoV-2 infection based on neutralizing antibody titers, researchers will further explore the levels of immune response required to achieve protection.

▲Role of the immune response triggered by viruses in suppressing viral proliferation (Image source: Reference [2])

BioNTech and Pfizer are also simultaneously expanding the production capacity of their candidate vaccines. If clinical trials prove successful and regulatory approval is obtained, the two companies estimate that they will be able to produce 100 million doses by the end of 2020, with potential capacity expansion to 1.2 billion doses by the end of 2021.

Currently, several candidate COVID-19 vaccines are on the verge of entering Phase III clinical development. We look forward to receiving positive updates from their clinical trials soon, thereby providing powerful tools to combat the COVID-19 pandemic.

References:

[1] Pfizer and BioNTech Announce Early Positive Data from an Ongoing Phase 1/2 Study of mRNA-based Vaccine Candidate Against SARS-CoV-2. Retrieved July 1, 2020from https://investors.biontech.de/news-releases/news-release-details/pfizer-and-biontech-announce-early-positive-data-ongoing-phase

[2] BNT162 COVID-19 Vaccine Update Call. Retrieved July 1, 2020, from https://investors.biontech.de/static-files/c4feb567-e564-40e5-a9cf-538892af1c04

[3] Mulligan et al., (2020). Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv, doi: https://doi.org/10.1101/2020.06.30.20142570

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