Recently published in SSRN, a large group of prominent New York City-based researchers recently completed a study thanks to the funding from NYU Grossman School of Medicine as well as grants, including multiple from the National Institutes of Health. Led by NYU’s Ellie Ivanova (Department of Pathology) and NYU Grossman School of Medicine’s Joseph Devlin (Institute of Systems Genetics), the team conducted a study called ‘Discrete Immune Response Signature to SARS-CoV-2 mRNA Vaccination Versus Infection,” investigating the impact of the Pfizer-BioNTech BNT162b2 mRNA vaccine as compared to natural immune response to the SARS-CoV-2 pathogen. While noting that both the mRNA vaccine and the virus itself triggers healthy and natural, not to mention adaptive, immune responses, the New York City-based scientists found “significant qualitative differences between the two types of immune challenges.” For example, the natural immune response, that is, an individual that fell ill from SARS-CoV-2 infection, recovering on their own could be “characterized by a highly augmented interferon response,” which for the most part didn’t materialize in vaccinated recipients. This and other deltas between the two responses lead to significant questions about the differences between vaccine-induced or natural immunity to SARS-Cov-2.
This recent study was uploaded to Elsevier’s SSRN as a not yet peer-reviewed manuscript. TrialSite provides a brief breakdown for the audience. What are the implications for this study? Could immune response to natural SARS-CoV-2 exposure be superior in human response as compared to vaccine antigen exposure?
This and all studies at NYU must be authorized by the NYU Institutional Review Board. All volunteers gave written informed consent in accordance with the Declaration of Helsinki.
The Basis for the Study
As reported in the authors’ manuscript, the authors point out that beyond antibody production, the knowledge behind COVID-19 vaccine immune response “remains largely uncharacterized.” Thus the authors sought out to provide more clarity to this important topic.
As described in their abstract, the study team conducted a study in a lab based on “multimodal single-cell sequencing on peripheral blood of patients with acute COVID-19” as well as a cohort of healthy volunteers before and after they received the mRNA vaccine known as BNT162bs developed by Pfizer-BioNTech.
Their mission: compare the immune response elicited by the natural pathogen and in parallel compare to the response triggered by the vaccine product in emergency use authorization (EUA). Then the investigational team employed phenotypic and transcriptional profiling of each of the patient samples’ immune cells along with “reconstruction of the B and T cell antigen receptor rearrangement of individual lymphocytes,” affording the team the opportunity to characterize and compare the host responses to both A) the virus and B) defined viral antigens.
Both the natural infection and mRNA vaccination-induced robust innate and adaptive responses but the authors noticed material differences in the two cohorts. TrialSite provides a brief table:
|Observation||Natural SARS-CoV-2 Infection||mRNA Vaccination|
|High augmented interferon response||High||Close to Absent|
|Dramatic upregulation of cytotoxic genes located in peripheral T cells & innate-like lymphocytes||High||Absent|
|Clonal B & T Cells||Effector Cells||Circulating Memory Cells|
The authors concluded that “far-reaching implications for immunity to SARS-CoV-2″ are implicated from their research: that is, the gap in two immune responses, transcriptional variance in the key immune populations, and the delta in maturation of adaptive immune cells call for further investigation.
- NYU Grossman School of Medicine
- National Institutes of Health (NIH) (multiple grants)
- Leo Foundation Grant
- NYU Cancer Center Pilot Grant
- Judith and Stewart Colton Center for Autoimmunity Pilot Grant
- Danish Cancer Society
Mark J. Mulligan, NYU Langone, works with Lilly and Pfizer (exclusive of the current work), as well as Sanofi for vaccines or mAb versus SARS-CoV-2. Fees from a firm called Meissa Vaccines Inc. and Pfizer for Scientific Advisory Board services.
Ivanova, Ellie and Devlin, Joseph and Buus, Terkild and Koide, Akiko and Cornelius, Amber and Samanovic, Marie and Herrera, Alberto and Zhang, Chenzhen and Desvignes, Ludovic and Odum, Niels and Ulrich, Robert and Mulligan, Mark J. and Koide, Shohei and Ruggles, Kelly V. and Herati, Ramin and Koralov, Sergei B.