TY - JOUR
T1 - Cross-reactivity of SARS-CoV-2- and influenza A-specific T cells in individuals exposed to SARS-CoV-2
AU - Chaisawangwong, Worarat
AU - Wang, Hanzhi
AU - Kouo, Theodore
AU - Salathe, Sebastian F.
AU - Isser, Ariel
AU - Bieler, Joan Glick
AU - Zhang, Maya L.
AU - Livingston, Natalie K.
AU - Li, Shuyi
AU - Horowitz, Joseph J.
AU - Samet, Ron E.
AU - Zyskind, Israel
AU - Rosenberg, Avi Z.
AU - Schneck, Jonathan P.
N1 - Funding Information:
This work was funded in part through NIH grants 3R33CA229042 and R33CA229042-S1 (to JPS), 5T32HD044355 (to TK), R01 EB029341 (to JPS), R33 CA229042 (to JPS), and P41 EB028239 (to JPS); National Science Foundation Graduate Research Fellowships 2016218370 (to AI) and 2018268995 (to NKL); and National Research Service Award fellowships (F31) 1F31CA254121-01A1 (to AI). The authors would like to thank the Larman laboratory for providing the RT-qPCR machine used, and all the donors for their generous participation in the study. We thank Hao Zhang and Joseph Margolick from the Flow Cytometry Cell Sorting Core Facility at Bloomberg School of Public Health, Johns Hopkins University, for performing FACS sorting. The facility is supported by NIH funding (1S10OD016315-01 and 1S10RR13777001, to Joseph Margolick) and, in part, by the Johns Hopkins Center for AIDS Research (5P30AI094189-04, to Richard Chaisson, Johns Hopkins University). We thank the NIH Tetramer Core Facility (contract 75N93020D00005) for providing tetramers.
Funding Information:
agreement between NexImmune and Johns Hopkins University, JPS and JGB are entitled to shares of royalties received by the university from sales of artificial antigen-presenting cell products described herein. JPS owns NexImmune stock, which is subject to certain restrictions under university policy and is a member of the company’s scientific advisory board. The terms of this arrangement are being managed by Johns Hopkins University, within the guidelines of its conflict-of-interest policies. JPS also acknowledges grant funding from AstraZeneca.
Publisher Copyright:
© 2022, Chaisawangwong et al.
PY - 2022/9/22
Y1 - 2022/9/22
N2 - Cross-reactive immunity between SARS-CoV-2 and other related coronaviruses has been welldocumented, and it may play a role in preventing severe COVID-19. Epidemiological studies early in the pandemic showed a geographical association between high influenza vaccination rates and lower incidence of SARS-CoV-2 infection. We, therefore, analyzed whether exposure to influenza A virus (IAV) antigens could influence the T cell repertoire in response to SARS-CoV-2, indicating a heterologous immune response between these 2 unrelated viruses. Using artificial antigen-presenting cells (aAPCs) combined with real-time reverse-transcription PCR (RT-qPCR), we developed a sensitive assay to quickly screen for antigen-specific T cell responses and detected a significant correlation between responses to SARS-CoV-2 epitopes and IAV dominant epitope (M158-66). Further analysis showed that some COVID-19 convalescent donors exhibited both T cell receptor (TCR) specificity and functional cytokine responses to multiple SARS-CoV-2 epitopes and M158-66. Utilizing an aAPC-based stimulation/expansion assay, we detected cross-reactive T cells with specificity to SARS-CoV-2 and IAV. In addition, TCR sequencing of the cross-reactive and IAV-specific T cells revealed similarities between the TCR repertoires of the two populations. These results indicate that heterologous immunity shaped by our exposure to other unrelated endemic viruses may affect our immune response to novel viruses such as SARS-CoV-2.
AB - Cross-reactive immunity between SARS-CoV-2 and other related coronaviruses has been welldocumented, and it may play a role in preventing severe COVID-19. Epidemiological studies early in the pandemic showed a geographical association between high influenza vaccination rates and lower incidence of SARS-CoV-2 infection. We, therefore, analyzed whether exposure to influenza A virus (IAV) antigens could influence the T cell repertoire in response to SARS-CoV-2, indicating a heterologous immune response between these 2 unrelated viruses. Using artificial antigen-presenting cells (aAPCs) combined with real-time reverse-transcription PCR (RT-qPCR), we developed a sensitive assay to quickly screen for antigen-specific T cell responses and detected a significant correlation between responses to SARS-CoV-2 epitopes and IAV dominant epitope (M158-66). Further analysis showed that some COVID-19 convalescent donors exhibited both T cell receptor (TCR) specificity and functional cytokine responses to multiple SARS-CoV-2 epitopes and M158-66. Utilizing an aAPC-based stimulation/expansion assay, we detected cross-reactive T cells with specificity to SARS-CoV-2 and IAV. In addition, TCR sequencing of the cross-reactive and IAV-specific T cells revealed similarities between the TCR repertoires of the two populations. These results indicate that heterologous immunity shaped by our exposure to other unrelated endemic viruses may affect our immune response to novel viruses such as SARS-CoV-2.
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U2 - 10.1172/jci.insight.158308
DO - 10.1172/jci.insight.158308
M3 - Article
C2 - 36134660
AN - SCOPUS:85138313172
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 18
M1 - e158308
ER -