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  1. Article ; Online: The Nucleocapsid Protein of SARS-CoV-2: a Target for Vaccine Development.

    Dutta, Noton K / Mazumdar, Kaushiki / Gordy, James T

    Journal of virology

    2020  Volume 94, Issue 13

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Nucleocapsid Proteins ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2
    Chemical Substances Nucleocapsid Proteins
    Keywords covid19
    Language English
    Publishing date 2020-06-16
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00647-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Accelerating Drug Development through Repurposed FDA-Approved Drugs for COVID-19: Speed Is Important, Not Haste.

    Gordy, James T / Mazumdar, Kaushiki / Dutta, Noton K

    Antimicrobial agents and chemotherapy

    2020  Volume 64, Issue 8

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus ; Coronavirus Infections ; Drug Development ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-07-22
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00857-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques.

    Luo, Kun / Gordy, James T / Zavala, Fidel / Markham, Richard B

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 1220

    Abstract: Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α ... ...

    Abstract Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system. In the current study, a squalene based adjuvant (AddaVax, InvivoGen, San Diego, Ca) equivalent to the clinically approved MF59 (Seqiris, Maidenhead, UK) elicited greater antibody responses in mice than the previously employed adjuvant polyinosinic:polycytidylic acid, ((poly(I:C), InvivoGen, San Diego, Ca) and the clinically approved Aluminum hydroxide gel (Alum, Invivogen, San Diego, Ca) adjuvant. Use of the AddaVax adjuvant also expanded the range of IgG subtypes elicited by mouse vaccination. Sera passively transferred into mice from MCSP/AddaVax immunized 1 and 6 month old macaques significantly reduced liver sporozoite load upon sporozoite challenge. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization. The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population.
    MeSH term(s) Adjuvants, Immunologic/pharmacology ; Animals ; Antibodies, Protozoan/immunology ; Antibody Formation/immunology ; Chemokines/immunology ; Dendritic Cells/immunology ; Dendritic Cells/parasitology ; Disease Models, Animal ; Female ; Immunization/methods ; Macaca/immunology ; Macaca/parasitology ; Malaria Vaccines/immunology ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Mice ; Mice, Inbred C57BL ; Plasmodium falciparum/immunology ; Poly I-C/immunology ; Protozoan Proteins/immunology ; Sporozoites/immunology ; Vaccination/methods
    Chemical Substances Adjuvants, Immunologic ; Antibodies, Protozoan ; Chemokines ; Malaria Vaccines ; Protozoan Proteins ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2021-01-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-79427-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques

    Kun Luo / James T. Gordy / Fidel Zavala / Richard B. Markham

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Abstract Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α ... ...

    Abstract Abstract Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system. In the current study, a squalene based adjuvant (AddaVax, InvivoGen, San Diego, Ca) equivalent to the clinically approved MF59 (Seqiris, Maidenhead, UK) elicited greater antibody responses in mice than the previously employed adjuvant polyinosinic:polycytidylic acid, ((poly(I:C), InvivoGen, San Diego, Ca) and the clinically approved Aluminum hydroxide gel (Alum, Invivogen, San Diego, Ca) adjuvant. Use of the AddaVax adjuvant also expanded the range of IgG subtypes elicited by mouse vaccination. Sera passively transferred into mice from MCSP/AddaVax immunized 1 and 6 month old macaques significantly reduced liver sporozoite load upon sporozoite challenge. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization. The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The Nucleocapsid Protein of SARS–CoV-2

    Dutta, Noton K. / Mazumdar, Kaushiki / Gordy, James T.

    Journal of Virology

    a Target for Vaccine Development

    2020  Volume 94, Issue 13

    Keywords Immunology ; Insect Science ; Microbiology ; Virology ; covid19
    Language English
    Publisher American Society for Microbiology
    Publishing country us
    Document type Article ; Online
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00647-20
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A SARS-CoV-2 RBD vaccine fused to the chemokine MIP-3α elicits sustained murine antibody responses over 12 months and enhanced lung T-cell responses.

    Gordy, James Tristan / Hui, Yinan / Schill, Courtney / Wang, Tianyin / Chen, Fengyixin / Fessler, Kaitlyn / Meza, Jacob / Li, Yangchen / Taylor, Alannah D / Bates, Rowan E / Karakousis, Petros C / Pekosz, Andrew / Sachithanandham, Jaiprasath / Li, Maggie / Karanika, Styliani / Markham, Richard B

    Frontiers in immunology

    2024  Volume 15, Page(s) 1292059

    Abstract: ... intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally ... immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs ... produced vaccine formulation to provide the extended antibody and T-cell responses that may be required ...

    Abstract Background: Previous studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN).
    Methods: BALB/c mice aged 6-8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α. In a small-scale (
    Results: At 12 months postprimary vaccination, recipients of the IM vaccine incorporating MIP-3α had significantly, approximately threefold, higher serum antibody concentrations than recipients of the vaccine not incorporating MIP-3α. The area-under-the-curve analyses of the 12-month observation interval demonstrated significantly greater antibody concentrations over time in recipients of the MIP-3α vaccine formulation. At 12 months postprimary immunization, only recipients of the fusion vaccine had concentrations of serum-neutralizing activity deemed to be effective. After intranasal immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs significantly above those of PBS controls. Low levels of serum antibody responses were obtained following IN immunization.
    Conclusion: Although requiring separate IM and IN immunizations for optimal immunization, incorporating MIP-3α in a SARS-CoV-2 vaccine construct demonstrated the potential of a stable and easily produced vaccine formulation to provide the extended antibody and T-cell responses that may be required for protection in the setting of emerging SARS-CoV-2 variants. Without electroporation, simple, uncoated plasmid DNA incorporating MIP-3α administered intranasally elicited lung T-cell responses.
    MeSH term(s) Animals ; Mice ; Antibody Formation ; Chemokines ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; DNA ; Lung ; SARS-CoV-2 ; T-Lymphocytes
    Chemical Substances Chemokines ; COVID-19 Vaccines ; DNA (9007-49-2)
    Language English
    Publishing date 2024-02-02
    Publishing country Switzerland
    Document type Journal Article ; 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.2024.1292059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Accelerating Drug Development through Repurposed FDA-Approved Drugs for COVID-19

    Gordy, James T. / Mazumdar, Kaushiki / Dutta, Noton K.

    Antimicrobial Agents and Chemotherapy

    Speed Is Important, Not Haste

    2020  Volume 64, Issue 8

    Keywords Pharmacology (medical) ; Pharmacology ; Infectious Diseases ; covid19
    Language English
    Publisher American Society for Microbiology
    Publishing country us
    Document type Article ; Online
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.00857-20
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Combination of a MIP3α-antigen fusion therapeutic DNA vaccine with treatments of IFNα and 5-Aza-2'Deoxycytidine enhances activated effector CD8+ T cells expressing CD11c in the B16F10 melanoma model.

    Fessler, Kaitlyn / Gordy, James T / Sandhu, Avinaash K / Hui, Yinan / Kapoor, Aakanksha R / Ayeh, Samuel K / Karanika, Styliani / Karakousis, Petros C / Markham, Richard B

    Research square

    2023  

    Abstract: ... CD8+ T cell population. This cell population correlates with tumor size, is primarily comprised ... of effector or effector memory T cells, and has a more robust response to ex vivo stimulation as compared ... to CD11c- CD8+ T cells as measured by surface activation markers 4-1BB (CD137) and KLRG1 ...

    Abstract Previous studies in the B16F10 mouse melanoma model have demonstrated that combining a DNA vaccine comprised of regions of gp100 and tyrosinase-related protein 2 fused to Macrophage-inflammatory protein 3-alpha (MIP3α) with recombinant Interferon alpha (IFN) and 5-Aza-2'-Deoxycytidine (5Aza) treatments resulted in significantly greater anti-tumor activity and immunogenicity in the tumor microenvironment (TME). This brief report details that the combination of vaccine with treatments IFN and 5Aza results in both the upregulation of genes expressing CD11c-interacting proteins and an increase in the TME of a distinct CD11c+ CD8+ T cell population. This cell population correlates with tumor size, is primarily comprised of effector or effector memory T cells, and has a more robust response to ex vivo stimulation as compared to CD11c- CD8+ T cells as measured by surface activation markers 4-1BB (CD137) and KLRG1 (Killer cell lectin-like receptor G1) and intracellular IFNγ production. In conclusion, this combination therapy results in greater presence of highly active effector CD8+ T-cells expressing CD11c in the TME that correlate with and are likely primary contributors to treatment efficacy.
    Language English
    Publishing date 2023-08-14
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3243336/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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