Messenger RNA Vaccines Against COVID-19 and its Variants

The novel messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) carry the genetic code the host cell needs to make the surface spike protein antigen to closely mimic a natural infection.1

To study the effectiveness of these vaccines, the US Centers for Disease Control and Prevention (CDC) conducted a longitudinal real-world study evaluating BNT162b2 and mRNA-1273 in nearly 4,000 healthcare professionals and first responders. Interim results show reduced risk of infection by 80% after partial vaccination, which fell to 90% after the second dose.2 These findings are similar to later stage trials showing that two-dose regimens of BNT162b2 and mRNA-1273 provide approximately 95% protection against COVID-19.3,4

Trials of mRNA vaccines were mainly conducted in the United States before variants of concern had been detected. Variants of concern are strains of SARS-CoV-2 that show evidence of increased transmissibility and/or disease severity and reduced effectiveness against therapies developed for prevention and treatment.5 These include the emergence of variants first identified in the United Kingdom (B.1.1.7, B.1.1.7+E48K), South Africa (B.1.351), Brazil (P.1), and California (B.1.427, B.1.429).
Much of the data of mRNA vaccine efficacy against new strains of the virus comes from laboratory models of SARS-CoV-2 variants. Serum samples from people immunized with BNT162b2 were exposed to genetically engineered versions of variants: B.1.1.7-spike, P.1-spike, and B.1.351-spike.6,7 This study showed approximately equivalent neutralizing antibodies of B.1.1.7-spike and P.1-spike, and robust but lower levels of neutralizing antibodies against B.1.351-spike.7

Serum samples of people who received mRNA-1273 were assayed against a recombinant vesicular stomatitis virus (rVSV)-based SARS-CoV-2 model of pseudoviruses carrying the strains B.1.1.7, B.1.351, P.1, B.1.427, B.1.429, B.1.1.7+E484K, and other variants.8 The study showed no significant effect on neutralization of B.1.1.7, but a decrease in titers of neutralizing antibodies against P.1, B.1.427, B.1.429, B.1.1.7+E484K, and B.1.351 variants.8


  1. Abbasi J. COVID-19 and mRNA vaccines—first large test for a new approach. JAMA. 2020;324(12):1125-1127.
  2. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — Eight U.S. Locations, December 2020-March 2021. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2021.
  3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603-2615.
  4. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403-416. 5. CDC. SARS-CoV-2 Variant Classifications and Definitions. Available at Accessed March 31, 2021.
  5. Rubin R. COVID-19 vaccines vs variants—determining how much immunity is enough. JAMA. Published online March 17, 2021. Accessed March 30, 2021.
  6. Liu Y, Liu J, Xia H, et al. Neutralizing activity of BNT162b2-elicited serum. N Engl J Med. March 8, 2021. DOI: 10.1056/NEJMc2102017