Principal Investigator

Rong
Fan
Awardee Organization

Yale University
United States

Fiscal Year
2024
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Immuno-Serological Assays for Monitoring COVID19 in Patients with Hematologic Malignancies

The main goals of the Supplement Award are to (1) correlate immunoserological responses to early immune reactions in local tissue environment of the vaccine injection site in healthy donors, and (2) the compare between healthy controls and patients with hematological disorders or autoimmune disease. We will use a high plex immuno-fluorescence CODEX imaging panel to profile these skin biopsy samples in the next year of the award. Using this panel, we can confirm the expression of the SARS-CoV-2 Spike antigen. Interestingly, the SARS-CoV2 Spike antigen was detected in the epidermis and dermis of both arms from two donors. Specifically, SARSCoV-2 Spike co-expressed with CD303 and CD63 of the unvaccinated arm tissue of a healthy donor and in cluster 0 of the vaccinated arm of a BCD donor, indicating expression in dendritic cells and basophils. In the next year to be supported by the Supplement Award, we will be imaging at least 13 more skin tissue sections and plan to conduct deeper informatics analysis. Additionally, we are performing DBiT-based spatial CITE-seq on adjacent slides from these 13 skin tissue sections and integrating the data with previously obtained sc-mRNAseq data. Furthermore, we have completed immunoserology assays with the serum samples of these donors and patients. Therefore, once we complete the peripheral tissue spatial imaging and spatial omics sequencing, the results will be compared to systemic immunological and serological responses over times to help understand the role of early immune reaction in the development of an effective vaccine protection, in particular, in patients with blood cancer or autoimmune disease.

Publications

  • Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan JM, Buitrago-Pocasangre NC, Lele N, Asashima H, Racke MK, Wilson JE, Givens TS, Tomayko MM, Schulz WL, Longbrake EE, Hafler DA, Halene S, Fan R. Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection. Small methods. 2023 Oct;7(10):e2300594. Epub 2023 Jun 13. PMID: 37312418
  • Figueiredo JC, Hirsch FR, Kushi LH, Nembhard WN, Crawford JM, Mantis N, Finster L, Merin NM, Merchant A, Reckamp KL, Melmed GY, Braun J, McGovern D, Parekh S, Corley DA, Zohoori N, Amick BC, Du R, Gregersen PK, Diamond B, Taioli E, Sariol C, Espino A, Weiskopf D, Gifoni A, Brien J, Hanege W, Lipsitch M, Zidar DA, Scheck McAlearney A, Wajnberg A, LaBaer J, Yvonne Lewis E, Binder RA, Moormann AM, Forconi C, Forrester S, Batista J, Schieffelin J, Kim D, Biancon G, VanOudenhove J, Halene S, Fan R, Barouch DH, Alter G, Pinninti S, Boppana SB, Pati SK, Latting M, Karaba AH, Roback J, Sekaly R, Neish A, Brincks AM, Granger DA, Karger AB, Thyagarajan B, Thomas SN, Klein SL, Cox AL, Lucas T, Furr-Holden D, Key K, Jones N, Wrammerr J, Suthar M, Yu Wong S, Bowman NM, Simon V, Richardson LD, McBride R, Krammer F, Rana M, Kennedy J, Boehme K, Forrest C, Granger SW, Heaney CD, Knight Lapinski M, Wallet S, Baric RS, Schifanella L, Lopez M, Fernández S, Kenah E, Panchal AR, Britt WJ, Sanz I, Dhodapkar M, Ahmed R, Bartelt LA, Markmann AJ, Lin JT, Hagan RS, Wolfgang MC, Skarbinski J. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies. Open forum infectious diseases. 2022 Apr 27;9(6):ofac171. doi: 10.1093/ofid/ofac171. eCollection 2022 Jun. PMID: 35765315
  • Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan JM, Buitrago-Pocasangre NC, Lele N, Asashima H, Racke MK, Wilson JE, Givens TS, Tomayko MM, Schulz WL, Longbrake EE, Hafler DA, Halene S, Fan R. Microfluidic immuno-serology assay revealed a limited diversity of protection against COVID-19 in patients with altered immunity. bioRxiv : the preprint server for biology. 2022 Sep 2. PMID: 36093346
  • Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature biotechnology. 2022 Jun;40(6):906-920. Epub 2021 Dec 17. PMID: 34921308
  • Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature. 2022 Jun;606(7914):585-593. Epub 2022 Apr 28. PMID: 35483404
  • Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre NC, Lutz R, Cruz I, Raddassi K, Ruff WE, Racke MK, Wilson JE, Givens TS, Grifoni A, Weiskopf D, Sette A, Kleinstein SH, Montgomery RR, Shaw AC, Li F, Fan R, Hafler DA, Tomayko MM, Longbrake EE. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI insight. 2023 Aug 22;8. (16). PMID: 37606046
  • Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature. 2022 Sep;609(7926):375-383. Epub 2022 Aug 17. PMID: 35978191