Randomized Controlled Trial
Study population and setting
This phase 1/2 trial was conducted in Germany as a part of “Project Lightspeed”, the joint BioNTech-Pfizer COVID-19 RNA vaccine development program. 60 healthy participants between the ages of 18 and 55 years old received the BNT162b1 vaccine, one of several candidates being tested in Project Lightspeed. Participants were divided into 5 groups of 12, receiving either 1, 10, 30, 50, or 60ug doses. All groups except for the 60ug group received a boost dose in addition to the priming dose. The aims of this trial were to expand upon findings from the US BNT162b1 trial, assessing safety and tolerability, and to characterize antibody and T-cell responses to the vaccine. Antibody response were examined at baseline, 7 and 21 days after the priming dose, and 7 and 21 days after the boosting dose, while T-cell responses were studied at baseline and after the boosting vaccination.
Summary of Main Findings
No serious adverse events were observed in any dose group. Reactogenicity symptoms including fever, chills, headache, muscle pain, joint pain, pain at injection site, and tenderness, were mild to moderate. Overall, symptoms were mild, dose-dependent, and transient. Participants showed strong, dose-dependent antibody responses post-vaccination, largely mirroring the results found in the US study, with levels comparable to or higher than those found in convalescent sera. When assessed by ELISpot assay, over 95% of participants receiving the prime-boost vaccination had robust, RBD-specific CD4+ T-cell responses with a Th1 polarization. Strong CD8+ T cell responses were detected, as well.
The results of this study were quite similar to those found in the US trial studying vaccine candidate BNT162b1, further enforcing their findings. No serious adverse events occurred, and no participants dropped out of the trial due to vaccine-related adverse events. The results of this study were also strengthened by the comparisons made to antibody levels found in convalescent sera samples.
As a constraint of phase 1 clinical trial design, there were small sample sizes per dose group in this study. Participants were also limited to those below 55 years old, and this vaccine will also need to be studied in older adults. Only two non-Caucasian participants were included in this study, highlighting the need to include a more diverse population in vaccine trials since a diverse population will be receiving a vaccine once one is approved. More in-depth analyses involving tissue resident T-cell populations and T-cell repertoires were not performed here due to small blood volumes available. Finally, persistence of the immune response was not studied here, but this will be analyzed after long-term follow up samples are collected in both the German and US trials.
Additional reporting on the BioNTech-Pfizer BNT162b1 RNA vaccine’s safety and tolerability, and induced antibody and T-cell responses.
This review was posted on: 16 October 2020