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Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 c...

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Autores principales: Chiuppesi, Flavia, Ortega-Francisco, Sandra, Gutierrez, Miguel-Angel, Li, Jing, Ly, Minh, Faircloth, Katelyn, Mack-Onyeike, Jada, La Rosa, Corinna, Thomas, Sandra, Zhou, Qiao, Drake, Jennifer, Slape, Cynthia, Fernando, Paolo, Rida, Wasima, Kaltcheva, Teodora, Grifoni, Alba, Sette, Alessandro, Patterson, Angela, Dempsey, Shannon, Ball, Brian, Ali, Haris, Salhotra, Amandeep, Stein, Anthony, Nathwani, Nitya, Rosenzweig, Michael, Nikolaenko, Liana, Al Malki, Monzr M., Dickter, Jana, Nanayakkara, Deepa D., Puing, Alfredo, Forman, Stephen J., Taplitz, Randy A., Zaia, John A., Nakamura, Ryotaro, Wussow, Felix, Diamond, Don J., Dadwal, Sanjeet S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538048/
https://www.ncbi.nlm.nih.gov/pubmed/37766168
http://dx.doi.org/10.3390/vaccines11091492
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author Chiuppesi, Flavia
Ortega-Francisco, Sandra
Gutierrez, Miguel-Angel
Li, Jing
Ly, Minh
Faircloth, Katelyn
Mack-Onyeike, Jada
La Rosa, Corinna
Thomas, Sandra
Zhou, Qiao
Drake, Jennifer
Slape, Cynthia
Fernando, Paolo
Rida, Wasima
Kaltcheva, Teodora
Grifoni, Alba
Sette, Alessandro
Patterson, Angela
Dempsey, Shannon
Ball, Brian
Ali, Haris
Salhotra, Amandeep
Stein, Anthony
Nathwani, Nitya
Rosenzweig, Michael
Nikolaenko, Liana
Al Malki, Monzr M.
Dickter, Jana
Nanayakkara, Deepa D.
Puing, Alfredo
Forman, Stephen J.
Taplitz, Randy A.
Zaia, John A.
Nakamura, Ryotaro
Wussow, Felix
Diamond, Don J.
Dadwal, Sanjeet S.
author_facet Chiuppesi, Flavia
Ortega-Francisco, Sandra
Gutierrez, Miguel-Angel
Li, Jing
Ly, Minh
Faircloth, Katelyn
Mack-Onyeike, Jada
La Rosa, Corinna
Thomas, Sandra
Zhou, Qiao
Drake, Jennifer
Slape, Cynthia
Fernando, Paolo
Rida, Wasima
Kaltcheva, Teodora
Grifoni, Alba
Sette, Alessandro
Patterson, Angela
Dempsey, Shannon
Ball, Brian
Ali, Haris
Salhotra, Amandeep
Stein, Anthony
Nathwani, Nitya
Rosenzweig, Michael
Nikolaenko, Liana
Al Malki, Monzr M.
Dickter, Jana
Nanayakkara, Deepa D.
Puing, Alfredo
Forman, Stephen J.
Taplitz, Randy A.
Zaia, John A.
Nakamura, Ryotaro
Wussow, Felix
Diamond, Don J.
Dadwal, Sanjeet S.
author_sort Chiuppesi, Flavia
collection PubMed
description Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3–12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty(®) (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4(+) T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty(®)-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations.
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spelling pubmed-105380482023-09-29 Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy Chiuppesi, Flavia Ortega-Francisco, Sandra Gutierrez, Miguel-Angel Li, Jing Ly, Minh Faircloth, Katelyn Mack-Onyeike, Jada La Rosa, Corinna Thomas, Sandra Zhou, Qiao Drake, Jennifer Slape, Cynthia Fernando, Paolo Rida, Wasima Kaltcheva, Teodora Grifoni, Alba Sette, Alessandro Patterson, Angela Dempsey, Shannon Ball, Brian Ali, Haris Salhotra, Amandeep Stein, Anthony Nathwani, Nitya Rosenzweig, Michael Nikolaenko, Liana Al Malki, Monzr M. Dickter, Jana Nanayakkara, Deepa D. Puing, Alfredo Forman, Stephen J. Taplitz, Randy A. Zaia, John A. Nakamura, Ryotaro Wussow, Felix Diamond, Don J. Dadwal, Sanjeet S. Vaccines (Basel) Article Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3–12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty(®) (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4(+) T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty(®)-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations. MDPI 2023-09-15 /pmc/articles/PMC10538048/ /pubmed/37766168 http://dx.doi.org/10.3390/vaccines11091492 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chiuppesi, Flavia
Ortega-Francisco, Sandra
Gutierrez, Miguel-Angel
Li, Jing
Ly, Minh
Faircloth, Katelyn
Mack-Onyeike, Jada
La Rosa, Corinna
Thomas, Sandra
Zhou, Qiao
Drake, Jennifer
Slape, Cynthia
Fernando, Paolo
Rida, Wasima
Kaltcheva, Teodora
Grifoni, Alba
Sette, Alessandro
Patterson, Angela
Dempsey, Shannon
Ball, Brian
Ali, Haris
Salhotra, Amandeep
Stein, Anthony
Nathwani, Nitya
Rosenzweig, Michael
Nikolaenko, Liana
Al Malki, Monzr M.
Dickter, Jana
Nanayakkara, Deepa D.
Puing, Alfredo
Forman, Stephen J.
Taplitz, Randy A.
Zaia, John A.
Nakamura, Ryotaro
Wussow, Felix
Diamond, Don J.
Dadwal, Sanjeet S.
Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title_full Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title_fullStr Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title_full_unstemmed Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title_short Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy
title_sort stimulation of potent humoral and cellular immunity via synthetic dual-antigen mva-based covid-19 vaccine coh04s1 in cancer patients post hematopoietic cell transplantation and cellular therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538048/
https://www.ncbi.nlm.nih.gov/pubmed/37766168
http://dx.doi.org/10.3390/vaccines11091492
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