Systems Vaccinology of BNT162b2mRNA Vaccine in Humans

Arunachalam, PS, Scott, MKD, Hagan, T., et al. Systems vaccinology of the BNT162b2mRNA vaccine in humans. Nature (2021). https://doi.org/10.1038/s41586-021-03791-x

Commentary

The two mRNA vaccines that were licensed for emergency use to deal with the SARS-CoV-2 outbreak appear to have been a milestone in vaccinology. However, the mechanism of how mRNA vaccines stimulate the immune system and induce a protective immune response is still unknown.

This study will use a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers vaccinated with Pfizer-BioNTechmRNA vaccine.

Vaccination resulted in strong production of neutralizing antibodies (nAbs) against the parental Uhan strain and, to a lesser extent, against the B.1.351 strain, and a significant increase in antigen-specific multifunctional CD4 and CD8 T cells after the second dose.

The booster vaccination was found to stimulate a significantly enhanced innate immune response compared to the primary vaccination.

(i) Frequency of CD14+CD16+ inflammatory monocytes; 

(ii) Concentration of plasma IFN-g; 

(iii) transcriptional signature of innate immunity.

Consistent with these observations, single-cell transcriptomic analysis showed an approximately 100-fold increase in the frequency of myeloid cell clusters rich in interferon-responsive transcription factors (TFs) and reduced in AP-1 TFs after secondary immunization.

Separate congenital pathways associated with CD8 T cell and nAb responses were identified, and monocyte-associated signatures were correlated with nAb responses to the B.1.351 mutant line. These data demonstrate the ability of mRNA vaccination to provide insight into the workings of the immune response and to stimulate the innate immune system to initiate a stronger response after booster immunization.