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Article ; Online: Synthetic modified vaccinia Ankara vaccines confer cross-reactive and protective immunity against mpox virus.

Chiuppesi, Flavia / Zaia, John A / Gutierrez-Franco, Miguel-Angel / Ortega-Francisco, Sandra / Ly, Minh / Kha, Mindy / Kim, Taehyun / Dempsey, Shannon / Kar, Swagata / Grifoni, Alba / Sette, Alessandro / Wussow, Felix / Diamond, Don J

Communications medicine

2024 Volume 4, Issue 1, Page(s) 19

Abstract: Background: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine ... ...

Abstract	Background: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. Methods: We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. Results: COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. Conclusions: These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00443-9
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Article ; Online: Transforming growth factor receptor III (Betaglycan) regulates the generation of pathogenic Th17 cells in EAE.

Duesman, Samuel J / Ortega-Francisco, Sandra / Olguin-Alor, Roxana / Acevedo-Dominguez, Naray A / Sestero, Christine M / Chellappan, Rajeshwari / De Sarno, Patrizia / Yusuf, Nabiha / Salgado-Lopez, Adrian / Segundo-Liberato, Marisol / de Oca-Lagunas, Selina Montes / Raman, Chander / Soldevila, Gloria

Frontiers in immunology

2023 Volume 14, Page(s) 1088039

Abstract: The transforming growth factor receptor III (TβRIII) is commonly recognized as a co-receptor that promotes the binding of TGFβ family ligands to type I and type II receptors. Within the immune system, TβRIII regulates T cell development in the thymus and ...

Abstract	The transforming growth factor receptor III (TβRIII) is commonly recognized as a co-receptor that promotes the binding of TGFβ family ligands to type I and type II receptors. Within the immune system, TβRIII regulates T cell development in the thymus and is differentially expressed through activation; however, its function in mature T cells is unclear. To begin addressing this question, we developed a conditional knock-out mouse with restricted TβRIII deletion in mature T cells, necessary because genomic deletion of TβRIII results in perinatal mortality. We determined that TβRIII null mice developed more severe autoimmune central nervous neuroinflammatory disease after immunization with myelin oligodendrocyte peptide (MOG
MeSH term(s)	Animals ; Female ; Mice ; Pregnancy ; Encephalitis ; Phosphorylation ; Receptors, Transforming Growth Factor beta/genetics ; Th17 Cells
Chemical Substances	betaglycan (145170-29-2) ; Receptors, Transforming Growth Factor beta
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1088039
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Article ; Online: Adoptive transfer of functional SARS-COV-2-specific immunity from donor graft to hematopoietic stem cell transplant recipients.

La Rosa, Corinna / Chiuppesi, Flavia / Park, Yoonsuh / Gendzekhadze, Ketevan / Zhou, Qiao / Faircloth, Katelyn / Kaltcheva, Teodora / Johnson, Daisy / Ortega Francisco, Sandra / Amanam, Idoroenyi / Otoukesh, Salman / Pullarkat, Vinod A / Nakamura, Ryotaro / Diamond, Don J / Forman, Stephen J / Al Malki, Monzr M

American journal of hematology

2022 Volume 97, Issue 11, Page(s) E404–E407

MeSH term(s)	Adoptive Transfer ; COVID-19 ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation ; Humans ; SARS-CoV-2
Language	English
Publishing date	2022-09-02
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26691
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Article: Inhibins regulate peripheral regulatory T cell induction through modulation of dendritic cell function

de la Fuente‐Granada, Marisol / Olguín‐Alor, Roxana / Ortega‐Francisco, Sandra / Bonifaz, Laura C. / Soldevila, Gloria

FEBS Open Bio. 2019 Jan., v. 9, no. 1

2019

Abstract: We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed‐type hypersensitivity responses. Here, we investigated the role of ... ...

Abstract	We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed‐type hypersensitivity responses. Here, we investigated the role of inhibins in peripheral regulatory T cell (Treg) induction in vitro and in vivo. Inhibin deficient (Inhα⁻/⁻) mice showed an increased percentage of peripherally induced Tregs in colonic lamina propria and mesenteric lymph nodes, compared to Inhα⁺/⁺ mice, which correlated with increased expression of PD‐L1 in CD103⁺ and CD8α⁺ DCs. Lipopolysaccharide‐stimulated bone marrow‐derived and ex vivo spleen‐ and lymph node‐purified CD11c⁺ Inhα⁻/⁻ DCs induced higher Tregs in vitro. Moreover, in vivo anti‐DEC205‐ovalbumin (OVA) DC targeting of mice with adoptively transferred OVA‐specific T cells showed enhanced induced peripheral Treg conversion in Inhα⁻/⁻ mice. These data identify inhibins as key regulators of peripheral T cell tolerance.
Keywords	T-lymphocytes ; delayed hypersensitivity ; dendritic cells ; inhibin ; lymph
Language	English
Dates of publication	2019-01
Size	p. 137-147.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12555
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Article: Inhibins regulate peripheral regulatory T cell induction through modulation of dendritic cell function.

de la Fuente-Granada, Marisol / Olguín-Alor, Roxana / Ortega-Francisco, Sandra / Bonifaz, Laura C / Soldevila, Gloria

FEBS open bio

2018 Volume 9, Issue 1, Page(s) 137–147

Abstract: We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed-type hypersensitivity responses. Here, we investigated the role of ... ...

Abstract	We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed-type hypersensitivity responses. Here, we investigated the role of inhibins in peripheral regulatory T cell (Treg) induction
MeSH term(s)	Animals ; Cells, Cultured ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Inhibins/deficiency ; Inhibins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Inhibins (57285-09-3)
Language	English
Publishing date	2018-12-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12555
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Article ; Online: Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants.

iScience

2022 Volume 25, Issue 8, Page(s) 104745

Abstract: Cell-mediated immunity may contribute to providing protection against SARS-CoV-2 and its variants of concern (VOC). We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara (MVA)-based COVID-19 vaccine that stimulated potent spike (S) and ... ...

Abstract	Cell-mediated immunity may contribute to providing protection against SARS-CoV-2 and its variants of concern (VOC). We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara (MVA)-based COVID-19 vaccine that stimulated potent spike (S) and nucleocapsid (N) antigen-specific humoral and cellular immunity in a phase 1 clinical trial in healthy adults. Here, we show that individuals vaccinated with COH04S1 or mRNA vaccine BNT162b2 maintain robust cross-reactive cellular immunity for six or more months post-vaccination. Although neutralizing antibodies induced in COH04S1- and BNT162b2-vaccinees showed reduced activity against Delta and Omicron variants compared to ancestral SARS-CoV-2, S-specific T cells elicited in both COH04S1- and BNT162b2-vaccinees and N-specific T cells elicited in COH04S1-vaccinees demonstrated potent and equivalent cross-reactivity against ancestral SARS-CoV-2 and the major VOC. These results suggest that vaccine-induced T cells to S and N antigens may constitute a critical second line of defense to provide long-term protection against SARS-CoV-2 VOC.
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104745
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Article ; Online: Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study.

La Rosa, Corinna / Chiuppesi, Flavia / Park, Yoonsuh / Zhou, Qiao / Yang, Dongyun / Gendzekhadze, Ketevan / Ly, Minh / Li, Jing / Kaltcheva, Teodora / Ortega Francisco, Sandra / Gutierrez, Miguel-Angel / Ali, Haris / Otoukesh, Salman / Amanam, Idoroenyi / Salhotra, Amandeep / Pullarkat, Vinod A / Aldoss, Ibrahim / Rosenzweig, Michael / Aribi, Ahmed M /

Stein, Anthony S / Marcucci, Guido / Dadwal, Sanjeet Singh / Nakamura, Ryotaro / Forman, Stephen J / Al Malki, Monzr M / Diamond, Don J

Frontiers in immunology

2023 Volume 14, Page(s) 1114131

Abstract: In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, ... ...

Abstract	In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide adequate protection to HCT recipients against infection with evolving SARS-CoV-2 variants. We performed a prospective observational study (NCT04666025 at ClinicalTrials.gov) to longitudinally monitor the transfer of SARS-CoV-2-specific antiviral immunity from HCT donors, who were either vaccinated or had a history of COVID-19, to their recipients Clinical trial registration: clinicaltrials.gov, identifier NCT04666025.
MeSH term(s)	Humans ; COVID-19 ; Hematopoietic Stem Cell Transplantation ; SARS-CoV-2 ; Tissue Donors ; Transplant Recipients ; T-Lymphocytes/immunology ; COVID-19 Vaccines
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-03-03
Publishing country	Switzerland
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1114131
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Article: TβRIII is induced by TCR signaling and downregulated in FoxP3+ regulatory T cells

Ortega-Francisco, Sandra / Chander Raman / Eduardo A. García-Zepeda / Evelyn K. Alvarez Salazar / Fernando López-Casillas / Gabriela Fonseca-Camarillo / Germán R. Alemán-Muench / Gloria Soldevila / Lizbeth Airais Bolaños-Castro / Marisol de la Fuente-Granada / Roxana Olguin-Alor

Biochemical and biophysical research communications. 2017 Dec. 09, v. 494, no. 1-2

2017

Abstract: TGF-β type III receptor (TβRIII) is a co-receptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-βs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins ... ...

Abstract	TGF-β type III receptor (TβRIII) is a co-receptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-βs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that TβRIII modulates T cell development by protecting developing thymocytes from apoptosis, however the role of this co-receptor in peripheral lymphocytes still remains elusive. Here we describe a detailed characterization of TβRIII expression in murine and human lymphocyte subpopulations demonstrating that this co-receptor is significantly expressed in T but not B lymphocytes and among them, preferentially expressed on naïve and central memory T cells. TβRIII was upregulated after TCR stimulation, in parallel to other early activation markers. In contrast, natural and induced Tregs downregulated TβRIII in association with FoxP3 upregulation. Finally, anti-TβRIII blocking experiments demonstrated that TβRIII promotes TGFβ-dependent iTreg conversion in vitro, and suggest that this co-receptor may be involved in modulating peripheral T cell tolerance and could be considered as a potential target to boost T cell immune responses.
Keywords	activins ; apoptosis ; B-lymphocytes ; bone morphogenetic proteins ; cell differentiation ; humans ; immune response ; ligands ; mice ; receptors ; thymocytes ; T-lymphocytes ; transforming growth factor beta
Language	English
Dates of publication	2017-1209
Size	p. 82-87.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2017.10.081
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Article: 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

2023 Volume 11, Issue 9

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 ... ...

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
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11091492
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Article: Towards the development of an epitope-focused vaccine for SARS-CoV-2

Cervantes-Torres, Jacquelynne / Rosales, Sergio / Cabello, Carlos / Montero, Laura / Hernandez-Aceves, Juan / Granados, Guillermo / Calderón-Gallegos, Arturo / Zúñiga-Flores, Francisco / Ruiz-Rivera, Mirna / César Abarca-Magaña, Julio / Ortega-Francisco, Sandra / Olguin-Alor, Roxana / Díaz, Georgina / Paczka-Garcia, Filipo / Zavala-Gaytan, Rubí / Vázquez-Ramírez, Ricardo / Adriana Ayón-Nuñez, Dolores / César Carrero, Julio / Rios, Diana /

Jasso-Ramírez, Mariana / Vázquez-Hernández, Rebeca / Venegas, David / Garzón, Daniel / Cobos, Laura / Segura-Velázquez, René / Villalobos, Nelly / Meneses, Gabriela / Zúñiga, Joaquín / Gamba, Gerardo / Cárdenas, Graciela / Hernández, Marisela / Parkhouse, Michael E / Romano, Marta C. / Alonso Herrera, Luis / Bobes, Raúl J. / Pérez-Tapia, Mayra / Huerta, Leonor / Fierro, Nora / Gracia, Isabel / Soldevilla, Gloria / Fragoso, Gladis / Suárez-Güemes, Francisco / Laclette, Juan P. / Sciutto, Edda

Vaccine. 2022 Sept. 20,

2022

Abstract: The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as ... ...

Abstract	The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.
Keywords	COVID-19 infection ; DNA ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; aluminum oxide ; epitopes ; immunogenicity ; mortality ; pandemic ; peptides ; subcutaneous injection ; vaccine development ; vaccines ; viruses
Language	English
Dates of publication	2022-0920
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2022.09.059
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