Systems vaccinology of the BNT162b2 mRNA vaccine in humans.
Prabhu S ArunachalamMadeleine K D ScottThomas HaganChunfeng LiYupeng FengFlorian WimmersLilit GrigoryanMeera TrisalVenkata-Viswanadh EdaraLilin LaiSarah Esther ChangAllan FengShaurya DhingraMihir ShahAlexandra S LeeSharon ChinthrajahSayantani B SindherVenkata Vamsee Aditya MallajosyulaFei GaoNatalia SigalSangeeta KowliSheena GuptaKathryn PellegriniGregory K TharpSofia Maysel-AuslenderSydney HamiltonHadj AouedKevin HrusovskyMark RoskeySteven E BosingerHolden T MaeckerScott D BoydMark M DavisPaul J UtzMehul S SutharPurvesh KhatriKari Christine NadeauBali PulendranPublished in: Nature (2021)
The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.
Keyphrases
- immune response
- dendritic cells
- sars cov
- single cell
- transcription factor
- binding protein
- toll like receptor
- rna seq
- wild type
- dengue virus
- emergency department
- public health
- healthcare
- respiratory syndrome coronavirus
- gene expression
- endothelial cells
- electronic health record
- high throughput
- bone marrow
- anti inflammatory
- mesenchymal stem cells
- inflammatory response