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  1. Article ; Online: Cytomegalovirus Triplex vaccine in pediatric hematopoietic stem cell transplant patients at high risk for cytomegalovirus complications: evaluation of vaccine safety, immunogenicity and impact on viremia requiring antivirals.

    La Rosa, Corinna / Park, Yoonsuh / Yang, Dongyun / Zhou, Qiao / Kaltcheva, Teodora / Karras, Nicole / Cheng, Jerry / Sun, Weili / Diamond, Don J / Pawlowska, Anna

    Haematologica

    2024  

    Abstract: Not available. ...

    Abstract Not available.
    Language English
    Publishing date 2024-02-29
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.284256
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform.

    Yll-Pico, Marcal / Park, Yoonsuh / Martinez, Joy / Iniguez, Angelina / Kha, Mindy / Kim, Taehyun / Medrano, Leonard / Nguyen, Vu H / Kaltcheva, Teodora / Dempsey, Shannon / Chiuppesi, Flavia / Wussow, Felix / Diamond, Don J

    NPJ vaccines

    2024  Volume 9, Issue 1, Page(s) 68

    Abstract: Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine ... ...

    Abstract Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.
    Language English
    Publishing date 2024-03-30
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-024-00859-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Natural killer cells contribute to enhanced respiratory disease after oil-in-water emulsion adjuvanted vaccination against respiratory syncytial virus and infection.

    Park, Yoonsuh / Kim, Ki-Hye / Lee, Youri / Lee, Young-Tae / Kang, Sang-Moo / Ko, Eun-Ju

    Human vaccines & immunotherapeutics

    2021  Volume 17, Issue 10, Page(s) 3806–3817

    Abstract: Respiratory syncytial virus (RSV) infection caused severe acute respiratory disease in children and the elderly. There is no licensed vaccine. It has been a challenging problem to avoid vaccine enhanced respiratory disease in developing a safe and ... ...

    Abstract Respiratory syncytial virus (RSV) infection caused severe acute respiratory disease in children and the elderly. There is no licensed vaccine. It has been a challenging problem to avoid vaccine enhanced respiratory disease in developing a safe and effective RSV vaccine. Here, we investigated the impact of MF59-like oil-in-water emulsion adjuvant Addavax on the vaccine efficacy of inactivated split RSV (sRSV) and the roles of natural killer (NK) cells in enhanced respiratory disease in sRSV vaccinated mice after RSV infection. Addavax-adjuvanted sRSV vaccination induced higher levels of IgG1 isotype antibodies and more effective lung viral clearance upon RSV infection but promoted enhanced respiratory disease of weight loss, pulmonary inflammation, and NK and NK T (NKT) cell infiltrations in the lungs. Antibody treatment depleting NK cells prior to RSV infection resulted in preventing severe weight loss and histopathology, as well as attenuating infiltration of dendritic cell subsets and TNF-α
    MeSH term(s) Animals ; Antibodies, Viral ; Emulsions ; Killer Cells, Natural ; Lung ; Mice ; Mice, Inbred BALB C ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Virus, Human ; Vaccination ; Water
    Chemical Substances Antibodies, Viral ; Emulsions ; Respiratory Syncytial Virus Vaccines ; Water (059QF0KO0R)
    Language English
    Publishing date 2021-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2664176-8
    ISSN 2164-554X ; 2164-5515
    ISSN (online) 2164-554X
    ISSN 2164-5515
    DOI 10.1080/21645515.2021.1915039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: BCG Cell Wall Skeleton As a Vaccine Adjuvant Protects Both Infant and Old-Aged Mice from Influenza Virus Infection.

    Kim, Ki-Hye / Lee, Young-Tae / Park, Yoonsuh / Ko, Eun-Ju / Jung, Yu-Jin / Kim, Yu-Jin / Jo, Eun-Kyeong / Kang, Sang-Moo

    Biomedicines

    2021  Volume 9, Issue 5

    Abstract: Bacillus Calmette-Guerin (BCG) and the cell wall skeleton (CWS) derived from BCG are known to enhance nonspecific immune activation and anti-cancer immunity; however, their roles as a vaccine adjuvant are largely unknown. Here, we report that BCG-CWS ... ...

    Abstract Bacillus Calmette-Guerin (BCG) and the cell wall skeleton (CWS) derived from BCG are known to enhance nonspecific immune activation and anti-cancer immunity; however, their roles as a vaccine adjuvant are largely unknown. Here, we report that BCG-CWS acts as a strong immune adjuvant by promoting the protective immune responses in mouse models with influenza vaccination. The different aged mice immunized with inactivated split vaccine with or without BCG-CWS were challenged with an influenza pandemic virus. When protective immune responses were compared, even a single immunization of adult mice with a BCG-CWS-adjuvanted vaccine showed significantly enhanced humoral immune responses with increased IgG1 and IgG2a isotype antibodies. Importantly, the protective effects by the BCG-CWS adjuvant for influenza vaccination upon humoral and cellular immunogenicity were comparable between infants (6 days and 2 weeks old) and aged (20 months old) mice. Moreover, BCG-CWS dramatically augmented vaccine-mediated protective responses, including decreased viral loads, lung damage, and airway resistance, as well as increased mouse survival, amelioration of weight loss, and proinflammatory cytokine expression in all experimental groups including infant, adults, and old aged mice. We further provided the evidence that the BCG-CWS adjuvant effects were mediated through Toll-like receptors (TLR) 2 and TLR4 signaling pathways. Together, these data suggest that BCG-CWS can be promising as a potential influenza vaccine adjuvant in both young and old aged population through TLR2/4-mediated immune-boosting activities.
    Language English
    Publishing date 2021-05-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines9050516
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis.

    La Rosa, Corinna / Aldoss, Ibrahim / Park, Yoonsuh / Yang, Dongyun / Zhou, Qiao / Gendzekhadze, Ketevan / Kaltcheva, Teodora / Rida, Wasima / Dempsey, Shannon / Arslan, Shukaib / Artz, Andrew / Ball, Brian / Nikolaenko, Liana / Pullarkat, Vinod A / Nakamura, Ryotaro / Diamond, Don J

    American journal of hematology

    2023  Volume 98, Issue 4, Page(s) 588–597

    Abstract: To enhance protective cytomegalovirus (CMV)-specific T cells in immunosuppressed recipients of an allogeneic hematopoietic cell transplant (HCT), we evaluated post-HCT impact of vaccinating healthy HCT donors with Triplex. Triplex is a viral vectored ... ...

    Abstract To enhance protective cytomegalovirus (CMV)-specific T cells in immunosuppressed recipients of an allogeneic hematopoietic cell transplant (HCT), we evaluated post-HCT impact of vaccinating healthy HCT donors with Triplex. Triplex is a viral vectored recombinant vaccine expressing three immunodominant CMV antigens. The vector is modified vaccinia Ankara (MVA), an attenuated, non-replicating poxvirus derived from the vaccinia virus strain Ankara. It demonstrated tolerability and immunogenicity in healthy adults and HCT recipients, in whom it also reduced CMV reactivation. Here, we report feasibility, safety, and immunological outcomes of a pilot phase 1 trial (NCT03560752 at ClinicalTrials.gov) including 17 CMV-seropositive recipients who received an HCT from a matched related donor (MRD) vaccinated with 5.1 × 10
    MeSH term(s) Adult ; Humans ; Cytomegalovirus ; Hematopoietic Stem Cell Transplantation/adverse effects ; CD8-Positive T-Lymphocytes ; Vaccinia/drug therapy ; Vaccinia/etiology ; Cytomegalovirus Infections/prevention & control ; Antiviral Agents/therapeutic use ; Vaccination
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2023-01-11
    Publishing country United States
    Document type Journal Article ; 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.26824
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: COH04S1 and beta sequence-modified vaccine protect hamsters from SARS-CoV-2 variants.

    Wussow, Felix / Kha, Mindy / Faircloth, Katelyn / Nguyen, Vu H / Iniguez, Angelina / Martinez, Joy / Park, Yoonsuh / Nguyen, Jenny / Kar, Swagata / Andersen, Hanne / Lewis, Mark G / Chiuppesi, Flavia / Diamond, Don J

    iScience

    2022  Volume 25, Issue 6, Page(s) 104457

    Abstract: COVID-19 vaccine efficacy is threatened by emerging SARS-CoV-2 variants of concern (VOC) with the capacity to evade protective neutralizing antibody responses. We recently developed clinical vaccine candidate COH04S1, a synthetic modified vaccinia Ankara ...

    Abstract COVID-19 vaccine efficacy is threatened by emerging SARS-CoV-2 variants of concern (VOC) with the capacity to evade protective neutralizing antibody responses. We recently developed clinical vaccine candidate COH04S1, a synthetic modified vaccinia Ankara vector (sMVA) co-expressing spike and nucleocapsid antigens based on the Wuhan-Hu-1 reference strain that showed potent efficacy to protect against ancestral SARS-CoV-2 in Syrian hamsters and non-human primates and was safe and immunogenic in healthy volunteers. Here, we demonstrate that intramuscular immunization of Syrian hamsters with COH04S1 and an analogous Beta variant-adapted vaccine candidate (COH04S351) elicits potent cross-reactive antibody responses and protects against weight loss, lower respiratory tract infection, and lung pathology following challenge with major SARS-CoV-2 VOC, including Beta and the highly contagious Delta variant. These results demonstrate efficacy of COH04S1 and a variant-adapted vaccine analog to confer cross-protective immunity against SARS-CoV-2 and its emerging VOC, supporting clinical investigation of these sMVA-based COVID-19 vaccine candidates.
    Language English
    Publishing date 2022-05-23
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104457
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Natural Killer and CD8 T Cells Contribute to Protection by Formalin Inactivated Respiratory Syncytial Virus Vaccination under a CD4-Deficient Condition.

    Ko, Eun-Ju / Lee, Youri / Lee, Young-Tae / Hwang, Hye Suk / Park, Yoonsuh / Kim, Ki-Hye / Kang, Sang-Moo

    Immune network

    2020  Volume 20, Issue 6, Page(s) e51

    Abstract: Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms ... ...

    Abstract Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.
    Language English
    Publishing date 2020-11-25
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2536191-0
    ISSN 2092-6685 ; 1598-2629
    ISSN (online) 2092-6685
    ISSN 1598-2629
    DOI 10.4110/in.2020.20.e51
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Successful outcome of pre-engraftment COVID-19 in an HCT patient: impact of targeted therapies and cellular immunity.

    Pourhassan, Hoda / La Rosa, Corinna / Chiuppesi, Flavia / Puing, Alfredo / Aldoss, Ibrahim / Park, Yoonsuh / Zhou, Qiao / Karpinski, Veronica / Faircloth, Katelyn / Kaltcheva, Teodora / Johnson, Daisy / Francisco, Sandra Ortega / Zaia, John A / Nakamura, Ryotaro / Al Malki, Monzr M / Diamond, Don J / Dadwal, Sanjeet Singh / Forman, Stephen J

    Blood advances

    2021  Volume 6, Issue 6, Page(s) 1645–1650

    Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell ... ...

    Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here, we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by reverse transcriptase polymerase chain reaction on day -1 of matched unrelated donor (SARS-CoV-2 immunoglobulin G negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient's nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2-specific T cells, starting early after transplant was unexpected, and in combination with the clinical strategy, may have contributed to the favorable outcome. Additionally, it is plausible that preexisting cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.
    MeSH term(s) COVID-19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunity, Cellular ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2021-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2021006282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants.

    Chiuppesi, Flavia / Zaia, John A / Faircloth, Katelyn / Johnson, Daisy / Ly, Minh / Karpinski, Veronica / La Rosa, Corinna / Drake, Jennifer / Marcia, Joan / Acosta, Ann Marie / Dempsey, Shannon / Taplitz, Randy A / Zhou, Qiao / Park, Yoonsuh / Ortega Francisco, Sandra / Kaltcheva, Teodora / Frankel, Paul H / Rosen, Steven / Wussow, Felix /
    Dadwal, Sanjeet / Diamond, Don J

    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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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