Pfizer and BioNTech announce early positive update from German phase 1/II COVID-19 vaccine study, of BNT 162 mRNA-based vaccine, including first T cell response data.

BioNTech SE and Pfizer Inc announced initial data from their ongoing German Phase 1/II, open-label, non-randomized, non-placebo-controlled, dose-escalation trial , that is part of the global mRNA-based vaccine program against SARS-CoV-2. The data are available on an online preprint server at medrxiv and are concurrently undergoing scientific peer-review for potential publication.

The preliminary clinical results are for the most advanced investigational vaccine candidate in Pfizer’s and BioNTech’s BNT162 mRNA-based vaccine program against SARS-CoV-2, BNT162b1. This vaccine candidate is a lipid nanoparticle formulated, nucleoside-modified messenger RNA that encodes an optimized SARS-CoV-2 receptor binding domain (RBD) antigen.

Overall, the new preliminary data from this German study support and expand upon the recently disclosed early results from the corresponding U.S. trial with BNT162b1. Preliminary data for BNT162b1 in the German Phase 1/II trial were evaluated with a total of 60 healthy adults 18 to 55 years of age enrolled in the study.

Of these 60 participants, 12 subjects per dose level (1 µg, 10 µg, 30 µg, and 50 µg; 48 participants in total) were vaccinated with BNT162b1 on day 1 and day 22 (n=12 per prime-boost cohort, except n=11 for the 10 µg and 50 µg cohorts from day 22 on). Furthermore, 12 participants received a single injection of 60 µg. The vaccine elicited high, dose level-dependent SARS-CoV-2-neutralizing titers and RBD-binding IgG concentrations after the second dose. Day 43 SARS-CoV-2 neutralizing geometric mean titers were in the range of 0.7-fold (1 µg) to 3.2-fold (50 µg) compared to that of a panel of SARS-CoV-2 infection convalescent human sera. Furthermore, sera of vaccinated subjects displayed broadly neutralizing activity in pseudovirus neutralization assays across a panel of sixteen SARS-CoV-2 RBD variants represented in publicly available SARS-CoV-2 sequences and against the newly dominant D614G strain. In addition, the initial German trial results demonstrate, for the first time for the BNT62b1 candidate, a concurrent induction of high level CD4+ and CD8+ T cell responses against the SARS-CoV-2 RBD.

The strength of T cell responses varied between subjects. There was no clear dose level dependency of the T cell response between 1 µg to 50 µg, indicating that stimulation and robust expansion of T cells might be accomplished at low mRNA dose levels.

All subjects in the prime-boost cohorts, except for two at the lowest dose level, had CD4+ T cell responses. Cytokine profiling of the RBD-specific CD4+ T cells demonstrated a TH1-dominant profile for these cells. 29 of the 36 tested subjects also mounted an RBD-specific functional, CD8+ T cell response that was comparable to memory responses observed against cytomegalovirus (CMV), Epstein Barr virus (EBV) and influenza virus.

Overall, the data suggested that BNT162b1 could potentially be administered safely, with a manageable tolerability profile. Local reactions and systemic events after injection with BNT162b1 at all dose levels were transient, generally mild to moderate, with occasional severe events (Grade 3) of flu-like symptoms and injection site reactions. All adverse events resolved spontaneously and were managed with simple measures. No serious adverse events (SAEs) were reported, and there were no withdrawals due to adverse events related to the vaccine.

Preliminary data from both the German and U.S. Phase 1/II studies, together with additional preclinical and clinical data being generated, will be used by the two companies to determine a dose level and select among multiple vaccine candidates to seek to progress to an anticipated large, global Phase IIb/III safety and efficacy trial. That trial may involve up to 30,000 healthy participants and is anticipated to begin in late July 2020, if regulatory approval is received.