Reactivity study: A collaboration between the Sette lab and Shane Crotty, Ph.D., to document acquired immunity to SARS-CoV-2 and help guide COVID-19 vaccine developers. Their May 2020 Cell study documents a robust antiviral immune response to SARS-CoV-2 in a group of 20 adults who had recovered from COVID-19. The findings show that the body’s immune system is able to recognize SARS-CoV-2 in many ways, dispelling fears that the virus may elude ongoing efforts to create an effective vaccine.

Cross-reactivity study: An investigation into the source of pre-existing T cell immune memory in people never exposed to SARS-CoV-2. The lab’s August Science study suggests that fighting off a common cold coronavirus can teach the T cell compartment to recognize some parts of SARS-CoV-2 and provides evidence for the hypothesis that common cold viruses can induce cross-reactive T cell memory against SARS-CoV-2. The research may explain why some people have milder COVID-19 cases than others—though this is speculation and much more data is needed.

Age and disease severity research: A collaboration with the lab of Shane Crotty, Ph.D., published in the Sept. 16, 2020 online issue of Cell, confirmed that a multi-layered, virus-specific immune response is important for controlling the virus during the acute phase of the infection and reducing COVID-19 disease severity, with the bulk of the evidence pointing to a much bigger role for T cells than antibodies. A weak or uncoordinated immune response, on the other hand, predicts a poor disease outcome. The findings suggested that vaccine candidates should aim to elicit a broad immune response that include antibodies, helper and killer T cells to ensure protective immunity.

Selected References
Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, Belanger S, Abbott RK, Kim C, Choi J, Kato Y, Crotty EG, Kim C, Rawlings SA, Mateus J, Tse LPV, Frazier A, Baric R, Peters B, Greenbaum J, Ollmann Saphire E, Smith DM, Sette A, Crotty S. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020 Sep 16:S0092-8674(20)31235-6. doi: 10.1016/j.cell.2020.09.038. Epub ahead of print. PMID: 33010815; PMCID: PMC7494270.

Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez S, Dan J, Burger Z, Rawlings S, Smith D, Phillips E, Mallal S, Lammers M, Rubiro P, Quiambao L, Sutherland A, Yu E, Da Silva Antunes R, Greenbaum, J, Frazier A, Markmann AJ, Premkumar L, de Silva A, Peters B, Crotty S, Sette A, Weiskopf D. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020 Aug 4:eabd3871. doi: 10.1126/science.abd3871. Epub ahead of print. PMID: 32753554.

Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA, Sutherland A, Premkumar L, Jadi RS, Marrama D, de Silva AM, Frazier A, Carlin AF, Greenbaum JA, Peters B, Krammer F, Smith DM, Crotty S, Sette A. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020 May 20:S0092-8674(20)30610-3. doi: 10.1016/j.cell.2020.05.015. Epub ahead of print. PMID: 32473127; PMCID: PMC7237901.

Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell Host Microbe. 2020 Apr 8;27(4):671-680.e2. doi: 10.1016/j.chom.2020.03.002. Epub 2020 Mar 16. PubMed PMID: 32183941; PubMed Central PMCID: PMC7142693.