NYU Scientists Study: Vaccines vs. Infection—Does Immunity Vary from Natural SARS-CoV-2 Infection to mRNA Vaccine?

NYU Scientists Study: Vaccines vs. Infection—Does Immunity Vary from Natural SARS-CoV-2 Infection to mRNA Vaccine?

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This recent study was uploaded to Elsevier’s SSRN as a not yet peer-reviewed manuscript.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?

Ethics Committee

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.

The Study

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.

Findings Summary

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:

ObservationNatural SARS-CoV-2 InfectionmRNA Vaccination
High augmented interferon responseHighClose to Absent
Dramatic upregulation of cytotoxic genes located in peripheral T cells & innate-like lymphocytesHighAbsent
Clonal B & T CellsEffector CellsCirculating 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.

Lead Research/Investigators

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.


  1. Let’s compare the study with a survey in India.


    “Two-thirds of India’s population have antibodies against the coronavirus, according to data released on Tuesday from a survey of 29,000 people across the nation conducted in June and July.”

    “The fourth national blood serum survey which tests for antibodies, known as a sero survey, included 8,691 children aged 6-17 years for the first time. Half of them were seropositive.”

    “The survey showed 67.6% of adults were seropositive, while more than 62% of adults were unvaccinated. As of July, just over 8% of eligible adult Indians had received two vaccine doses.”

    “About 400 million of India’s 1.4 billion people did not have antibodies, the survey showed.”

    “India’s daily cases have fallen to four-month lows after a second-wave that crippled the healthcare system…”
    “…The study also surveyed 7,252 healthcare workers and found 85% had antibodies, with one in 10 unvaccinated.”

    The mixed situation of vaccinated/natural in India is a place to learn about SARS-CoV-2 variant contagion and several more things.

    What effect did the use of ivermectin have

    What will the vaccine do for the variant

    What will natural immunity do for lowering the spread of all SARS-CoV-2 variants

    What are the differences between vaccinated immunity and COVID-19 recovered natural immunity