During the pandemic, research has moved at an unprecedented pace, culminating in several successful vaccines curtailing the global crisis. In this webinar, Dr. Prabhu S. Arunachalam of Stanford University, presents the efforts of the Pulendran lab to comprehensively profile human immune responses to SARS-CoV-2 infection and mRNA vaccination. Using a systems biological approach, he will demonstrate an impaired peripheral innate immune response in severe COVID-19 patients. Mechanisms underlying severe COVID-19 disease progression and potential therapeutic targets for COVID-19 will be revealed.

 

Recently, Dr. Arunachalam used a similar approach to evaluate immune responses induced by the Pfizer-BioNTech mRNA (BNT162b2) vaccine. Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 and the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Strikingly, the second vaccination also stimulated an enhanced innate immune response as compared to primary vaccination, akin to memory responses seen in B and T cells.

 

Consistent with these observations, single-cell transcriptomics analysis using the 10x Genomics platform 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. 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.

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