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Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Our take —

The findings in this study demonstrated that the BNT162b2 vaccine was safe and immunogenic, including in a population of older adults. Results were promising for use of the BNT162b2 vaccine in older adults, and findings indicated that a second dose provided benefit by increasing neutralizing antibody titers. The 30ug dose of BNT162b2 with a 2-dose strategy will be tested in a larger phase 2/3 study in a more diverse population.

Study design

Randomized Controlled Trial

Study population and setting

This phase 1 trial was conducted at four sites in the US between May 4 and June 22, 2020. The trial included participants between the ages of 18 and 55 years, as well as 65 to 85 years. Two vaccines were being tested: BNT162b1, which encodes the RBD, and BNT162b2, which encodes the full-length spike protein. Groups of 15 participants received 10, 20, 30 or 100ug doses, with 3/15 participants receiving placebo. All groups except for the 100ug groups received two doses of vaccine 21 days apart. The primary outcome was safety, and the secondary outcome was immunogenicity, with humoral responses being examined and compared to convalescent serum samples.

Summary of Main Findings

Results of BNT162b1 were previously reported from German and US trials in younger adults, so this summary will focus on the results in the older adult participants. Mild-to-moderate pain at injection site was reported from BNT162b1 in older participants, but no older participants had redness or swelling from BNT162b2. Mild systemic events resulted from BNT162b1, including headache and fatigue, and some reported a fever after second dose. Milder systemic events followed vaccination with BNT162b2, with a smaller proportion reporting fever. No severe systemic events occurred in the older adults group. Fewer participants used antipyretics or pain medication following BNT162b2 than BNT162b1. Similar serologic responses from were achieved from BNT162b1 and BNT162b2, with neutralizing antibody titers increasing especially following second dose. Older adults had less IgG and neutralizing antibodies compared to the younger adults, but still more than convalescent serum samples. Due to less reactogenicity but similar immunogenicity, the 30ug BNT162b2 moved on to phase 2/3 trials internationally.

Study Strengths

This study compared serological results to those from convalescent serum samples, and also examined two different mRNA vaccine designs. Older adults were included in the study, and the prime-boost dosing strategy was also tested to demonstrate the benefit of a second dose.

Limitations

Only antibody based immune responses, but not cellular immune responses, were studied here. Though antibody titers were higher than those found in convalescent serum samples, how much protection this will lend against COVID-19 and how long the protection will last is unknown at this time. There were not enough participants for statistical power, nor was there enough diversity in participants.

Value added

Insight into safety and immunogenicity of BioNTech and Pfizer’s BNT162b1 and BNT162b2 vaccines in older adults, and rationale for choosing BNT162b2 to move onto phase 2/3 trials.

This review was posted on: 2 November 2020