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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.
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.
Afiliación
  • Chiuppesi F; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Ortega-Francisco S; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Gutierrez MA; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Li J; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Ly M; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Faircloth K; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Mack-Onyeike J; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • La Rosa C; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Thomas S; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Zhou Q; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Drake J; Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Slape C; Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Fernando P; Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Rida W; Independent Researcher, Arlington, VA 22205, USA.
  • Kaltcheva T; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Grifoni A; Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, University of California San Diego, La Jolla, CA 92037, USA.
  • Sette A; Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, University of California San Diego, La Jolla, CA 92037, USA.
  • Patterson A; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Dempsey S; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Ball B; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Ali H; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Salhotra A; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Stein A; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Nathwani N; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Rosenzweig M; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Nikolaenko L; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Al Malki MM; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Dickter J; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Nanayakkara DD; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Puing A; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Forman SJ; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Taplitz RA; Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Zaia JA; Department of Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Nakamura R; Center for Gene Therapy, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Wussow F; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Diamond DJ; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Dadwal SS; Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Vaccines (Basel) ; 11(9)2023 Sep 15.
Article en En | MEDLINE | ID: mdl-37766168
ABSTRACT
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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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2023 Tipo del documento: Article