What is the mechanism of action of the Pfizer (Comirnaty) COVID-19 vaccine?

Mechanism of Action of the Pfizer (Comirnaty) COVID-19 Vaccine

The Pfizer-BioNTech COVID-19 vaccine (Comirnaty) uses messenger RNA (mRNA) technology that delivers genetic instructions to cells, resulting in temporary expression of the SARS-CoV-2 spike protein, which then triggers an immune response against the virus. 1

Core Mechanism

• The vaccine contains mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2, encapsulated within lipid nanoparticles for delivery into cells 1
• Once injected, the lipid nanoparticles facilitate the entry of mRNA into host cells, where cellular machinery translates the mRNA into the SARS-CoV-2 spike protein 1
• The expressed spike protein appears on the cell surface, where it is recognized by the immune system as a foreign antigen 1
• This recognition triggers both humoral (antibody) and cellular immune responses against the spike protein 1

Immune Response Generated

• The vaccine induces production of neutralizing antibodies that target the spike protein, preventing SARS-CoV-2 from binding to and entering human cells 1
• T-cell responses are also generated, which provide additional protection through cellular immunity 1
• The immune memory created provides protection against future SARS-CoV-2 infection, particularly against severe disease 1

Bivalent Booster Formulation

• The newer bivalent booster versions of the Pfizer vaccine contain mRNA encoding spike proteins from both:
  • The original Wuhan-hu-1 (ancestral) strain
  • The Omicron BA.4/BA.5 sublineages 1
• This bivalent approach aims to expand immune protection against currently circulating Omicron variants while maintaining protection against the original strain 1

Technical Aspects

• Unlike traditional vaccines that use weakened or inactivated viruses, mRNA vaccines do not contain any live virus components 1
• The mRNA does not enter the cell nucleus or interact with DNA, and is degraded shortly after protein production 1
• The lipid nanoparticle delivery system is crucial for protecting the fragile mRNA molecules and facilitating cellular uptake 2
• After the spike protein is produced, it is processed and fragments are presented on the cell surface via MHC molecules, activating the adaptive immune response 1

Safety Considerations

• As the vaccine does not contain live virus, it cannot cause COVID-19 infection 1
• The mRNA is degraded within days, leaving no permanent genetic material in the body 1
• Reactogenicity (expected immune responses like fever, pain at injection site) is common but typically mild and transient 1
• Myocarditis has been reported as a rare adverse event, particularly in young males, but the benefit-to-risk ratio remains strongly favorable 1

Efficacy

• In clinical trials, the original Pfizer-BioNTech vaccine demonstrated 95% efficacy in preventing symptomatic COVID-19 infection 1
• Protection against severe disease remains high even with the emergence of variants, though effectiveness against infection has waned over time with newer variants 1
• Bivalent boosters were developed specifically to address the immune evasion capabilities of the Omicron variant 1, 3

The mRNA vaccine technology allows for rapid adaptation to new variants by simply modifying the genetic sequence encoded in the mRNA, which is a key advantage in responding to an evolving virus like SARS-CoV-2 4.