NEW YORK & MAINZ, Germany—Pfizer Inc. and BioNTech SE recently reported preliminary preclinical data in mouse and non-human primate models from their BNT162b2 mRNA-based vaccine program against SARS-CoV-2.
In a non-human primate preclinical study, immunization with BNT162b2—a nucleoside-modified messenger RNA (modRNA) candidate—protected rhesus macaques against SARS-CoV-2 infection. The manuscript describing these preclinical data is available on the preprint server bioRxiv. It is concurrently undergoing peer-review for potential publication.
“The data we have shared ... include the characterization of our lead candidate BNT162b2, as well as key animal studies that were the basis for our clinical programs. They have enabled us to advance BNT162b2 into Phase 3 evaluation,” said Dr. Ugur Sahin, co-founder and CEO of BioNTech. “This is another development milestone for providing a safe and effective potential vaccine to the global community to help end this pandemic.”
In the preclinical study, BNT162b2 demonstrated protective antiviral effects in rhesus macaques, with high neutralizing antibody titers and a TH1-biased cellular response in rhesus macaques and mice. Both macaques that received two injections with 100 µg BNT162b2 and those that received saline control injections were challenged 55 days after the second immunization with a high viral inoculum of SARS-CoV-2 via intranasal and intratracheal routes.
Immunization with BNT162b2 reduced viral infection, with no viral RNA detected in the lower respiratory tract of the immunized animals. In most control animals, there was evidence of viral RNA.
BNT162b2 vaccination elicited a high frequency of CD4+ T cells that produced IFN-?, IL-2, and TNF-α, and almost no IL-4 producing CD4+ cells were detectable. This indicates a TH1-biased response, an immune profile thought to promote vaccine safety. BNT162b2 also elicited spike-specific IFN-?-producing CD8+ T cell responses, thought to promote an antiviral effect.
In a preclinical murine model, a single intramuscular immunization of BNT162b2 (0.2, 1, or 5 µg) generated B cell and T cell immune responses in BALB/c mice, and SARS-CoV-2 pseudovirus neutralizing activity increased steadily to day 28—the last day for which titers are reported.
CD4+ and CD8+ T cells from splenocytes isolated from BNT162b2-immunized mice were strongly positive for IFN-? and IL-2, producing high levels of the TH1 cytokines but minute amounts of TH2 cytokines. This suggests a robust, TH1-biased T cell adaptive immune response.
“Collectively, these preclinical results, combined with our clinical data collected to date, continue to support the promise and validity of our mRNA-based vaccine program against SARS-CoV-2 and selection of the BNT162b2 candidate, which we believe has the potential to prevent many millions of COVID-19 cases,” commented Dr. Kathrin U. Jansen, senior vice president and head of vaccine research and development at Pfizer.
These preclinical data and the Phase 1 clinical results influenced the decision by Pfizer and BioNTech to commence the global (apart from China) Phase 2/3 safety and efficacy portion of the clinical study to evaluate potential prevention of COVID-19 disease by BNT162b2. The Phase 2/3 study has enrolled participants 18 to 85 years of age in the United States, Argentina and Brazil. Additional enrollment is planned in Germany, Turkey and South Africa.
Assuming clinical success, BioNTech and Pfizer are on track to seek regulatory review for BNT162b2 as early as October of this year. If regulatory authorization is obtained, the companies plan to supply up to 100 million doses worldwide by the end of 2020, and approximately 1.3 billion doses by the end of 2021.
In other related news, Pfizer and BioNTech recently submitted an amended protocol to the U.S. Food and Drug Administration to expand the enrollment of their Phase 3 vaccine trial to approximately 44,000 participants. This will allow for the enrollment of new populations.
A press release from September 12 noted that trial enrollment has been proceeding as planned, and the trial expected to soon reach its initial target of 30,000 participants. The proposed expansion would allow the companies to further increase trial population diversity to include adolescents as young as 16 years of age, as well as people with stable HIV, hepatitis C or hepatitis B infection. The expansion would also provide additional safety and efficacy data.
Pfizer and BioNTech also announced that they have concluded exploratory talks with the European Commission for a proposed supply of 200 million doses of their investigational BNT162 mRNA-based vaccine candidate against SARS-CoV-2 to European Union member states, with an option for 100 million further doses. Deliveries would start by the end of 2020, subject to clinical success and regulatory authorization. The companies are now entering into contract negotiations with the European Commission.
“Pfizer and BioNTech’s anticipated agreement with the European Commission is an important step forward in our shared goal to have millions of doses of a vaccine against COVID-19 available for vulnerable populations before the end of the year. We would like to thank the European Commission for its commitment and confidence in our development efforts,” stated Albert Bourla, chairman and CEO of Pfizer. “We have activated our supply chain, most importantly our site in Belgium, and are starting to manufacture so that our vaccine would be available as soon as possible if our clinical trials prove successful and regulatory approval is granted.”