Program Official

Principal Investigator

Carlos A
Sariol
Awardee Organization

University Of Puerto Rico Med Sciences
United States

Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

SARS-CoV-2 correlates of protection in a Latino-origin population

The rapid global spread of SARS-CoV-2 has had a significant impact on the cancer population. SARSCoV-2 infection of hematopoietic stem cell transplant (HSCT) recipients leads to a poor prognosis with a ~68% survival rate. Immune mediated protection is critical to protect the HSCT population. However, there are significant gaps in our understanding of vaccine induced immune responses in the HSCT patient population. This proposed research will greatly advance our understanding of 1) mRNA vaccine driven immune responses in immune compromised subject populations, and 2) the functionality of the SARS-CoV-2 antigen specific T and B cell response in the HSCT population; 3) the role of the adaptive immune response in controlling breakthrough infections. The results of this proposal will have both short and long-term impacts. In the short term we will define a series of critical parameters that could improve the quality of life of HSCT patients during the pandemic. These studies will define the immunogenicity of mRNA SARS-CoV-2 vaccines before and after boosters. In two cohorts we will surveil for asymptomatic and symptomatic SARS-CoV-2 infections and evaluate the level of vaccine immunity close to the time of the breakthrough infection. In the long-term the SARS-CoV-2 pandemic was the 3rd global transmission of a novel coronavirus in the past 20 years. It is likely that there will be outbreaks in the future with currently unknown coronaviruses, and thus it is critical to determine now how high-risk groups respond to vaccination and if they require frequent booster vaccinations or potentially higher vaccine doses. Given the speed and efficacy of the mRNA vaccine platform, it is highly likely that the use of this vaccine platform will be expanded to combat other known pathogens, but also could be used to combat any range of potential emerging viral pathogens. The strength, breadth, and durability of responses to mRNA vaccines needs to be determined in different risk groups in longitudinal cohorts now, in order to prepare for future epidemics/pandemics.

Publications

  • Bowen JE, Addetia A, Dang HV, Stewart C, Brown JT, Sharkey WK, Sprouse KR, Walls AC, Mazzitelli IG, Logue JK, Franko NM, Czudnochowski N, Powell AE, Dellota E Jr, Ahmed K, Ansari AS, Cameroni E, Gori A, Bandera A, Posavad CM, Dan JM, Zhang Z, Weiskopf D, Sette A, Crotty S, Iqbal NT, Corti D, Geffner J, Snell G, Grifantini R, Chu HY, Veesler D. Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. Science (New York, N.Y.). 2022 Aug 19;377(6608):890-894. Epub 2022 Jul 19. PMID: 35857529
  • Tarke A, Sidney J, Methot N, Yu ED, Zhang Y, Dan JM, Goodwin B, Rubiro P, Sutherland A, Wang E, Frazier A, Ramirez SI, Rawlings SA, Smith DM, da Silva Antunes R, Peters B, Scheuermann RH, Weiskopf D, Crotty S, Grifoni A, Sette A. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell reports. Medicine. 2021 Jul 20;2(7):100355. Epub 2021 Jul 2. PMID: 34230917
  • Martel F, Cuervo-Rojas J, Ángel J, Ariza B, González JM, Ramírez-Santana C, Acosta-Ampudia Y, Murcia-Soriano L, Montoya N, Cardozo-Romero CC, Valderrama-Beltrán SL, Cepeda M, Castellanos JC, Gómez-Restrepo C, Perdomo-Celis F, Gazquez A, Dickson A, Brien JD, Mateus J, Grifoni A, Sette A, Weiskopf D, Franco MA. Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population. Frontiers in immunology. 2023 Jul 27;14:1241038. doi: 10.3389/fimmu.2023.1241038. eCollection 2023. PMID: 37575243
  • Pinski AN, Steffen TL, Zulu MZ, George SL, Dickson A, Tifrea D, Maroney KJ, Tedeschi N, Zhang Y, Scheuermann RH, Pinto AK, Brien JD, Messaoudi I. Corticosteroid treatment in COVID-19 modulates host inflammatory responses and transcriptional signatures of immune dysregulation. Journal of leukocyte biology. 2021 Dec;110(6):1225-1239. Epub 2021 Nov 3. PMID: 34730254
  • Tarke A, Sidney J, Methot N, Zhang Y, Dan JM, Goodwin B, Rubiro P, Sutherland A, da Silva Antunes R, Frazier A, Rawlings SA, Smith DM, Peters B, Scheuermann RH, Weiskopf D, Crotty S, Grifoni A, Sette A. Negligible impact of SARS-CoV-2 variants on CD4 + and CD8 + T cell reactivity in COVID-19 exposed donors and vaccinees. bioRxiv : the preprint server for biology. 2021 Mar 1. PMID: 33688655
  • da Silva Antunes R, Pallikkuth S, Williams E, Dawen Yu E, Mateus J, Quiambao L, Wang E, Rawlings SA, Stadlbauer D, Jiang K, Amanat F, Arnold D, Andrews D, Fuego I, Dan JM, Grifoni A, Weiskopf D, Krammer F, Crotty S, Hoffer ME, Pahwa SG, Sette A. Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers. The Journal of infectious diseases. 2021 Jul 2;224(1):70-80. PMID: 33822097
  • Sariol CAA, Pantoja P, Serrano-Collazo C, Rosa-Arocho T, Armina-Rodríguez A, Cruz L, Stone ETT, Arana T, Climent C, Latoni G, Atehortua D, Pabon-Carrero C, Pinto AKK, Brien JDD, Espino AMM. Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination. Viruses. 2021 Sep 30;13. (10). PMID: 34696403
  • da Silva Antunes R, Pallikkuth S, Williams E, Yu ED, Mateus J, Quiambao L, Wang E, Rawlings SA, Stadlbauer D, Jiang K, Amanat F, Arnold D, Andrews D, Fuego I, Dan JM, Grifoni A, Weiskopf D, Krammer F, Crotty S, Hoffer ME, Pahwa SG, Sette A. Differential T cell reactivity to seasonal coronaviruses and SARS-CoV-2 in community and health care workers. medRxiv : the preprint server for health sciences. 2021 Jan 15. PMID: 33469594
  • Rodríguez-Martinó E, Medina-Prieto R, Santana-Bagur J, Santé M, Pantoja P, Espino AM, Sariol CA, Torres EA. Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators. medRxiv : the preprint server for health sciences. 2021 Sep 15. PMID: 34545370
  • Sariol CA, Serrano-Collazo C, Ortiz EJ, Pantoja P, Cruz L, Arana T, Atehortua D, Pabon-Carrero C, Espino AM. Limited impact of Delta variant’s mutations in the effectiveness of neutralization conferred by natural infection or COVID-19 vaccines in a Latino population. medRxiv : the preprint server for health sciences. 2021 Oct 26. PMID: 34729566
  • Tarke A, Sidney J, Kidd CK, Dan JM, Ramirez SI, Yu ED, Mateus J, da Silva Antunes R, Moore E, Rubiro P, Methot N, Phillips E, Mallal S, Frazier A, Rawlings SA, Greenbaum JA, Peters B, Smith DM, Crotty S, Weiskopf D, Grifoni A, Sette A. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell reports. Medicine. 2021 Feb 16;2(2):100204. Epub 2021 Jan 26. PMID: 33521695
  • Bowen JE, Sprouse KR, Walls AC, Mazzitelli IG, Logue JK, Franko NM, Ahmed K, Shariq A, Cameroni E, Gori A, Bandera A, Posavad CM, Dan JM, Zhang Z, Weiskopf D, Sette A, Crotty S, Iqbal NT, Corti D, Geffner J, Grifantini R, Chu HY, Veesler D. Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines. bioRxiv : the preprint server for biology. 2022 Mar 16. PMID: 35313570
  • King RG, Silva-Sanchez A, Peel JN, Botta D, Dickson AM, Pinto AK, Meza-Perez S, Allie SR, Schultz MD, Liu M, Bradley JE, Qiu S, Yang G, Zhou F, Zumaquero E, Simpler TS, Mousseau B, Killian JT Jr, Dean B, Shang Q, Tipper JL, Risley CA, Harrod KS, Feng T, Lee Y, Shiberu B, Krishnan V, Peguillet I, Zhang J, Green TJ, Randall TD, Suschak JJ, Georges B, Brien JD, Lund FE, Roberts MS. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge. Vaccines. 2021 Aug 9;9. (8). PMID: 34452006
  • Geerling E, Pinski AN, Stone TE, DiPaolo RJ, Zulu MZ, Maroney KJ, Brien JD, Messaoudi I, Pinto AK. Roles of antiviral sensing and type I interferon signaling in the restriction of SARS-CoV-2 replication. iScience. 2022 Jan 21;25(1):103553. Epub 2021 Dec 3. PMID: 34877479
  • Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science (New York, N.Y.). 2021 Feb 5;371. (6529). Epub 2021 Jan 6. PMID: 33408181
  • Zhang Z, Mateus J, Coelho CH, Dan JM, Moderbacher CR, Gálvez RI, Cortes FH, Grifoni A, Tarke A, Chang J, Escarrega EA, Kim C, Goodwin B, Bloom NI, Frazier A, Weiskopf D, Sette A, Crotty S. Humoral and cellular immune memory to four COVID-19 vaccines. Cell. 2022 Jul 7;185(14):2434-2451.e17. Epub 2022 May 27. PMID: 35764089
  • López-Marte P, Soto-González A, Ramos-Tollinchi L, Torres-Jorge S, Ferre M, Rodríguez-Martinó E, Torres EA, Sariol CA. Inefficient Induction of Neutralizing Antibodies against SARS-CoV-2 Variants in Patients with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy after Receiving a Third mRNA Vaccine Dose. Vaccines. 2022 Aug 11;10. (8). PMID: 36016189
  • Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to eight months after infection. bioRxiv : the preprint server for biology. 2020 Dec 18. PMID: 33442687
  • Sariol CA, Pantoja P, Serrano-Collazo C, Rosa-Arocho T, Armina A, Cruz L, Stone ET, Arana T, Climent C, Latoni G, Atehortua D, Pabon-Carrero C, Pinto AK, Brien JD, Espino AM. Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike protein after natural infection or COVID-19 vaccination. medRxiv : the preprint server for health sciences. 2021 Aug 10. PMID: 34100029