Phase I/II Clinical Trial Results from COVID-19 RNA based SARS-CoV-2 Vaccine BNT162b1 in Adults

Phase I/II Clinical Trial Results from COVID-19 RNA based SARS-CoV-2 Vaccine BNT162b1 in Adults BNT162b1 

BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. BNT162b1 is one of several RNA-based SARS-CoV-2 vaccine candidates. Data shows that up to 14 days after a second dose in adults (18–55 years of age) from an ongoing phase I/II vaccine study with BNT162b1, which is also enrolling adults who are 65–85 years of age. Possible side effects included only all local reactions which were mild or moderate in severity, except for one report of severe pain after the first dose of 100 μg BNT162b1. Other symptoms reported in the 7 days after each vaccination in both BNT162b1 and placebo groups were mild to moderate fatigue and headache. The largest changes were decreases in the lymphocyte count after the first dose in 8.3% (1 out of 12), 45.5% (5 out of 11) and 50.0% (6 out of 12) of participants who received 10 μg, 30 μg and 100 μg BNT162b1, respectively. One participant each in the 10-μg (8.3% (1 out of 12)) and 30-μg (9.1% (1 out of 11)) groups and 4 participants in the 100-μg group (33.3% (4 out of 12)) had grade 3 decreases.    

For all doses, small increases in SARS-CoV-2-neutralizing geometric mean titres (GMTs) were observed 21 days after the first dose. Overall, robust immunogenicity was observed after vaccination with BNT162b1. Neutralization provides a measure of the vaccine-elicited antibody response that is more relevant to potential protection. RNA-based prophylactic infectious-disease vaccines and RNA therapeutic agents have been shown to be safe and well-tolerated in clinical trials. Vaccination with RNA elicits a robust innate immune response. RNA directs the expression of the vaccine antigen in host cells and has intrinsic adjuvant effects. RNA-vaccine manufacturing platform—irrespective of the encoded pathogen antigen—is the ability to rapidly produce large quantities of vaccine doses against a new pathogen. Safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. 

Overall local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR.