Safety of Two RNA-Based COVID-19 Vaccine Candidates

Dec 17, 2020
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Authors:
Walsh EE, Frenck RW Jr, Falsey AR, et al.
Citation:
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med 2020;383:2439-2450.
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • This analysis reports that the immune responses elicited by both BNT162b1 and BNT162b2 were similar.
  • As has been observed with other vaccines, the immunogenicity of the two vaccine candidates decreased with age, eliciting lower overall humoral responses in adults 65-85 years of age than in those 18-55 years of age.
  • Antibody responses in both younger and older adults showed a clear benefit of a second dose.
 

Study Questions:

What is the safety and immunogenicity of two RNA-based coronavirus disease 2019 (COVID-19) vaccine candidates?

Methods:

The investigators randomly assigned healthy adults 18-55 years of age and those 65-85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation in an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose.

Results:

A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and three received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples.

Conclusions:

The authors concluded that the safety and immunogenicity data from this US phase 1 trial of two vaccine candidates in younger and older adults added to earlier interim safety, and immunogenicity data support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.

Perspective:

This analysis reports that the immune responses elicited by both BNT162b1 and BNT162b2 were similar. As has been observed with other vaccines, the immunogenicity of the two vaccine candidates decreased with age, eliciting lower overall humoral responses in adults 65-85 years of age than in those 18-55 years of age. Nevertheless, at 7 days and 14 days after the second dose, the 50% and 90% neutralizing geometric mean titers elicited by 30 μg of BNT162b2 in older adults exceeded those of the convalescent serum panel. Antibody responses in both younger and older adults showed a clear benefit of a second dose. An ongoing trial of two doses of 30 μg of BNT162b2 in up to 44,000 participants from diverse backgrounds will provide additional robust safety and efficacy data.

Clinical Topics: COVID-19 Hub, Dyslipidemia, Geriatric Cardiology, Prevention, Lipid Metabolism

Keywords: Antibody Formation, Coronavirus, COVID-19, Geriatrics, Immune System Phenomena, Lipids, Nanoparticles, Primary Prevention, RNA, RNA, Messenger, severe acute respiratory syndrome coronavirus 2, Vaccination, Vascular Diseases, Viral Vaccines


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