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Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults

Our take —

This Phase 1/2, placebo controlled study provides encouraging preliminary evidence that the COVID-19 RNA vaccine candidate (BNT162b1) is well tolerated and elicits an immune response at least comparable to antibody levels observed in a panel of convalescent plasma. This study suggests that a 10ug – 30ug dose of this vaccine candidate could be effective. This is a Phase 1 study, and as such is done with limited participant numbers. Larger Phase 2 and Phase 3 trials are still required to fully evaluate the efficacy of this vaccine candidate. Additionally, continued monitoring of participants will be done to evaluate safety and immune response over time.

Preprint Review

This expert summary is for the peer-reviewed article linked above. We also summarized this paper before it underwent peer-review.  You can find the original review of the preprint by clicking here.

Study design

Randomized Controlled Trial

Study population and setting

Phase 1/2 placebo-controlled, observer-blind study to determine the best dose of vaccine candi-date BNT162b1 based on safety, tolerability, immunogenicity and potential efficacy. This study is ongoing. Data from 45 participants is presented. Participants were mostly white (82.2.%) non-Hispanic/non-Latino (93.3%) healthy males (51.1%) and non-pregnant females (48.9%) age 18-55 years. Twelve participants received either a 10ug or 30ug vaccine dose on day 1 and 21. An additional twelve participants received a single dose of 100ug of vaccine.

Summary of Main Findings

The safety and tolerability profile of this vaccines is similar to that seen with other RNA-based vaccines, including pain at the injection site, mild to moderate fatigue, headache, and fever. Based on the reactogenicity of the first dose of 100ug, a second dose was not administered. Adverse events were reported by 50% of participants in the 10ug and 30ug dose group and by 58.3% of participants in the 100ug group. No severe adverse advents were reported. Serum antibody titers in all groups were significantly higher than those seen in a panel of COVID-19 convalescent human sera by 21 days post-first vaccination. Neutralizing antibody titers in all groups were 1.8 to 2.8-fold higher than a panel of COVID-19 convalescent human sera. Following the second dose, serum antibody titers specific to the receptor binding domains of SARS-CoV-2 spike protein were 8.0 to 50 fold higher than those found in a convalescent serum panel, and neutralizing antibody titers were 1.9 to 4.6 fold higher. This study suggests that a 10ug – 30ug dose of this vaccine candidate could be effective.

Study Strengths

This study was placebo controlled and monitored appropriate markers for safety and tolerability. Comparison of antibody titers to convalescent serum is helpful for understanding the magnitude of the immune response elicited by the vaccine candidate.

Limitations

There is no known correlate of protection for SARS-CoV-2 infection. While comparisons to convalescent plasma are informative, it is still unknown what types and magnitude of immune response is required for protection against SARS-CoV-2 infection. Continued monitoring of participants is ongoing and will be necessary to understand the safety and durability of the immune response beyond 2 weeks post-vaccination. This trial only included participants as old as 55 years of age. As older populations are at higher risk, the results from safety and immunogenicity studies in populations 55 and older will be required and are on-going. Additionally, this is part of a larger phase 1 trial including a total of 4 different vaccine candidates, but results from only one candidate trial are reported here. This study is ongoing.

Value added

This study provides encouraging preliminary evidence that the COVID-19 RNA vaccine candidate (BNT162b1) is well tolerated and elicits an immune response at least comparable to antibody levels observed in a panel of convalescent plasma.

This review was posted on: 24 August 2020