Vaccines (Sep 2023)
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
- Flavia Chiuppesi,
- Sandra Ortega-Francisco,
- Miguel-Angel Gutierrez,
- Jing Li,
- Minh Ly,
- Katelyn Faircloth,
- Jada Mack-Onyeike,
- Corinna La Rosa,
- Sandra Thomas,
- Qiao Zhou,
- Jennifer Drake,
- Cynthia Slape,
- Paolo Fernando,
- Wasima Rida,
- Teodora Kaltcheva,
- Alba Grifoni,
- Alessandro Sette,
- Angela Patterson,
- Shannon Dempsey,
- Brian Ball,
- Haris Ali,
- Amandeep Salhotra,
- Anthony Stein,
- Nitya Nathwani,
- Michael Rosenzweig,
- Liana Nikolaenko,
- Monzr M. Al Malki,
- Jana Dickter,
- Deepa D. Nanayakkara,
- Alfredo Puing,
- Stephen J. Forman,
- Randy A. Taplitz,
- John A. Zaia,
- Ryotaro Nakamura,
- Felix Wussow,
- Don J. Diamond,
- Sanjeet S. Dadwal
Affiliations
- Flavia Chiuppesi
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Sandra Ortega-Francisco
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Miguel-Angel Gutierrez
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Jing Li
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Minh Ly
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Katelyn Faircloth
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Jada Mack-Onyeike
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Corinna La Rosa
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Sandra Thomas
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Qiao Zhou
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Jennifer Drake
- Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA
- Cynthia Slape
- Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA
- Paolo Fernando
- Clinical Trials Office, City of Hope National Medical Center, Duarte, CA 91010, USA
- Wasima Rida
- Independent Researcher, Arlington, VA 22205, USA
- Teodora Kaltcheva
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Alba Grifoni
- Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, University of California San Diego, La Jolla, CA 92037, USA
- Alessandro Sette
- Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, University of California San Diego, La Jolla, CA 92037, USA
- Angela Patterson
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Shannon Dempsey
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Brian Ball
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Haris Ali
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Amandeep Salhotra
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Anthony Stein
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Nitya Nathwani
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Michael Rosenzweig
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Liana Nikolaenko
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Monzr M. Al Malki
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Jana Dickter
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Deepa D. Nanayakkara
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Alfredo Puing
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Stephen J. Forman
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Randy A. Taplitz
- Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA 91010, USA
- John A. Zaia
- Center for Gene Therapy, City of Hope National Medical Center, Duarte, CA 91010, USA
- Ryotaro Nakamura
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Felix Wussow
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Don J. Diamond
- Department of Hematology and HCT, Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
- Sanjeet S. Dadwal
- Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA 91010, USA
- DOI
- https://doi.org/10.3390/vaccines11091492
- Journal volume & issue
-
Vol. 11,
no. 9
p. 1492
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.
Keywords
- SARS-CoV-2
- modified vaccinia Ankara (MVA)
- spike
- nucleocapsid
- hematopoietic cell transplantation (HCT)
- immunosuppression
