• Mon - Sat 8:00 - 6:30, Sunday - CLOSED

BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

The effect of the SARS-CoV-2 pandemic has necessitated the rapid development of safe and effective prophylactic vaccines. Eleven months after starting ‘Project Lightspeed’ (the joint BioNTech–Pfizer programme for the development of an RNA vaccine for COVID-19), BNT162b2 became the first vaccine to be authorized for emergency use. The vaccine showed 95% efficacy for protection against COVID-19 in a phase-II/III trial1 and emerging real-world data confirm that BNT162b2 is highly effective in preventing COVID-19 and hospitalization and death associated with SARS-CoV-2 infection3,4,5. The observational data also demonstrate that BNT162b2 reduces laboratory-confirmed infection, as well as viral load in individuals who are infected3,4,5,6.

BNT162b2 is based on lipid-nanoparticle-formulated mRNA vaccine technology, which delivers precise genetic information of the immunogen to antigen-presenting cells and elicits potent immune responses7. mRNA is transiently expressed, does not integrate into the genome and is degraded by physiological pathways. mRNA vaccines are molecularly well-defined and synthesized efficiently from DNA templates by in vitro transcription8,9,10. mRNA production and lipid nanoparticle formulation are fast and highly scalable, which renders this technology suitable for the rapid development and supply of vaccines during pandemic scenarios11,12.

BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

Two phase-I/II umbrella trials, one in Germany and one in the USA, investigated four candidate RNA–lipid nanoparticle vaccines. Preliminary clinical data from these studies on two candidates, BNT162b113,14 and BNT162b22, have previously been reported. Both of the candidates are pharmacologically optimized15,16, N1-methylpseudouridine nucleoside-modified mRNAs17 that are administered intramuscularly in a prime–boost regimen 21 days apart. BNT162b1 encodes a trimerized, secreted version of the receptor-binding domain (RBD) of S, whereas BNT162b2 encodes full-length SARS-CoV-2 S stabilized in the prefusion conformation18. BNT162b2 was selected as pivotal candidate on the basis of the totality of data obtained in the two phase-I/II trials and challenge studies in non-human primates2,18.

In the phase-I/II trial in the USA (NCT04368728), immunization with BNT162b2 at dose levels of up to 30 μg was associated with generally mild-to-moderate local reactions at the injection site as well as systemic events, such as fatigue, headache and myalgia2. Robust concentrations of S1-binding immunoglobulin G (IgG) and neutralizing titres against a SARS-CoV-2 strain with the wild-type (Wuhan-Hu-1) S sequence were elicited. Geometric mean 50% neutralizing titres (GMTs) of sera drawn from younger (18–55 years) and older (65–85 years) adults seven days after the booster dose of 30 μg BNT162b2 were 3.8-fold and 1.6-fold, respectively, the GMT of samples from individuals who had recovered from COVID-19. Here we provide data from the phase-I/II trial in Germany (NCT04380701, EudraCT: 2020-001038-36) that provide insights into vaccine-induced immune responses after prime–boost vaccination with 1, 10, 20 and 30 μg BNT162b2 in participants of 19–55 years of age. In addition to reporting neutralizing-antibody GMTs up to day 85 after dose 1 and cross-neutralizing-antibody GMTs against newly emerging SARS-CoV-2 strains, this study provides a characterization of the T cell responses elicited by BNT162b2, including the identification of epitopes that are recognized by the CD8+ T cells induced by a COVID-19 vaccine.