How AstraZeneca Johnson & Johnson and Pfizer Vaccines Activate Innate Immunity Through Different Technologies
The AstraZeneca, Johnson & Johnson, and Pfizer COVID-19 vaccines employ different technologies, and their mechanisms of activating innate immunity also differ. Here is a detailed overview of the adjuvants or components that help activate the innate immune system for each of these vaccines:
AstraZeneca (Vaxzevria, formerly AZD1222)
Technology: Viral vector vaccine (chimpanzee adenovirus vector, ChAdOx1)
Innate Immune Activation
Mechanism: The AstraZeneca vaccine uses a replication-deficient chimpanzee adenovirus vector (ChAdOx1) to deliver the gene encoding the SARS-CoV-2 spike protein. When the viral vector enters human cells, it induces the production of the spike protein, which triggers an immune response.
Innate Immune Activation: The viral vector itself acts as a natural adjuvant. Adenoviruses are known to activate the innate immune system through the recognition by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), specifically TLR9, and by stimulating the inflammasome pathways.
This results in the production of type I interferons and other pro-inflammatory cytokines, enhancing the overall immune response.
Johnson & Johnson (Janssen, Ad26.COV2.S)
Technology: Viral vector vaccine (human adenovirus vector, Ad26)
Innate Immune Activation
Mechanism: The Johnson & Johnson vaccine uses a replication-incompetent human adenovirus type 26 (Ad26) vector to deliver the SARS-CoV-2 spike protein gene. The spike protein produced by host cells triggers an immune response.
Innate Immune Activation: Similar to the AstraZeneca vaccine, the Ad26 vector itself acts as an adjuvant. The adenovirus vector activates the innate immune system through PRRs, particularly TLRs, and the inflammasome pathways. This activation results in the release of cytokines and chemokines, promoting a robust immune response.
Pfizer-BioNTech (Comirnaty, BNT162b2)
Technology: mRNA vaccine
Innate Immune Activation
Mechanism: The Pfizer-BioNTech vaccine uses lipid nanoparticles (LNPs) to deliver mRNA encoding the SARS-CoV-2 spike protein into human cells. The cells use this mRNA to produce the spike protein, which then elicits an immune response.
Innate Immune Activation: The mRNA and the lipid nanoparticles (LNPs) themselves play a role in activating the innate immune system:mRNA: mRNA can be recognized by PRRs such as TLR3, TLR7, and TLR8, which detect single-stranded RNA. This recognition triggers the production of type I interferons and other pro-inflammatory cytokines.
Lipid Nanoparticles (LNPs): The LNPs help protect the mRNA and facilitate its delivery into cells. They can also be recognized by the innate immune system, leading to the activation of PRRs and subsequent production of cytokines and chemokines.
Summary
AstraZeneca: Uses a chimpanzee adenovirus vector (ChAdOx1), which activates the innate immune system through PRRs and inflammasome pathways, producing type I interferons and pro-inflammatory cytokines.
Johnson & Johnson: Uses a human adenovirus vector (Ad26), which similarly activates the innate immune system through PRRs and inflammasome pathways, enhancing the immune response.
Pfizer-BioNTech: Utilizes mRNA delivered by lipid nanoparticles (LNPs). The mRNA is recognized by TLRs (TLR3, TLR7, TLR8), and the LNPs also stimulate innate immune responses, leading to the production of type I interferons and pro-inflammatory cytokines.
These mechanisms ensure a strong and effective immune response by engaging both the innate and adaptive immune systems.
