Pfizer and BioNTech Provide Data from German Phase 1/2 Study Further Characterizing Immune Response Following Immunization with Lead COVID-19 Vaccine Candidate BNT162b2

Pfizer Inc. and BioNTech SE announced additional data on neutralizing antibody and T cell responses from the Phase 1/2 trial with BNT162b2 conducted in Germany. The study results demonstrate that BNT162b2 elicits a combined adaptive humoral and cellular immune response against SARS-CoV-2 and provide insights into the composite nature of BNT162b2-induced T cell immunity. The results were published on the preprint server MedRxiv and are available here. BNT162b2 is an investigational COVID-19 vaccine developed by Pfizer-BioNTech. It has been authorized for emergency use for individuals 16 years of age and older in several countries around the world.

“In parallel to working with regulators around the globe to make our vaccine available, we will continue to share important data from our ongoing studies with the global scientific community and the public in order to advance our collective understanding of the underlying vaccine mechanism of action,” said Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. “While there is a broad consensus that vaccines should induce antibody responses against the virus, experiences from the prior SARS pandemic indicate that CD8+ T cell responses may be of critical importance to achieve long-term protection.”

“These results from the ongoing German Phase 1/2 study help illustrate the multiple arms of the immune system that are activated to fight SARS-CoV-2 by the vaccine candidate BNT162b2. Advancing the understanding of the duration of antibody responses is critical as the global scientific community continues to look for potential vaccines to help overcome this pandemic,” said Kathrin U. Jansen, Ph.D., Senior Vice President and Head of Vaccine Research & Development at Pfizer. “We continue to add to the body of scientific evidence supporting BNT162b2 and are pleased to see the consistency in our findings across studies.”.”

The ongoing non-randomized open-label Phase 1/2 trial (NCT04380701) is being conducted in Germany in parallel to the Phase 1/2/3 trial (NCT04368728) that started in the U.S. The German study evaluated the safety and immunogenicity of BNT162b2 in different dose cohorts (1 µg, 10 µg, 20 µg and 30 µg) with 11-12 participants per cohort. BNT162b2 was administered in two doses 21 days apart to healthy adults between 18 and 55 years of age.

Overall, these results mirror those from the U.S. study (NCT04368728) that were previously published, and support the favorable safety profile and robust induction of virus-specific antibody responses. A longer follow-up period of 85 days showed sustained neutralizing antibody titers in the range of, or above, those in convalescent sera cohort. BNT162b2 immune sera efficiently neutralized 19 pseudo-viruses, indicating the potential for broad BNT162b2-elicited protection against reported mutations.

All 37 participants vaccinated with BNT162b2 showed newly generated spike protein-specific CD4+ T cell responses, and almost 92% of participants demonstrated CD8+ T cell responses. The majority were strong T cell responses comparable to or significantly higher than memory responses of the same individuals against common viruses, such as cytomegalovirus (CMV), Epstein Barr virus (EBV) and the influenza virus. Even with the lowest dose of 1 µg BNT162b2, most of the vaccinated participants elicited robust expansion of CD4+ and CD8+ T cells. Expression of cytokines IFNγ and IL-2, but only low levels of IL-4 in BNT162b2-induced CD4+ T cells indicated a TH1 profile. CD8+ T cell responses were directed against multiple regions of the spike protein, and several of the multiple epitopes recognized by BNT162b2-induced CD8+ T cells were molecularly identified.

Effectors of the adaptive immune system have complementary roles in defense against viral infections. While neutralizing antibodies are the first line of defense, CD8+ T cells contribute to virus clearance from intracellular compartments that are inaccessible to neutralizing antibodies. Antigen-specific CD4+ T cells have immune orchestrating functions, including support of memory generation. Therefore, detailed characterization of the cellular immune responses will be important in understanding the mechanisms contributing to protection against SARS-CoV-2.

As of today, BNT162b2, Pfizer-BioNTech Covid-19 vaccine candidate, has been authorized or approved for emergency use for individuals 16 years of age and older in the U.S, U.K., Bahrain, Canada, Saudi Arabia, and Mexico. Pfizer and BioNTech have submitted a final Conditional Marketing Authorization Application (CA) following rolling submissions with the European Medicines Agency (EMA) and several other regulatory agencies around the world.