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  1. Article: Human plasma cells engineered to secrete bispecifics drive effective

    Hill, Tyler F / Narvekar, Parnal / Asher, Gregory / Camp, Nathan / Thomas, Kerri R / Tasian, Sarah K / Rawlings, David J / James, Richard G

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long- ... ...

    Abstract Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long-term
    Language English
    Publishing date 2023-08-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.24.554523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Primary and Secondary Dengue Virus Infections Elicit Similar Memory B-Cell Responses, but Breadth to Other Serotypes and Cross-Reactivity to Zika Virus Is Higher in Secondary Dengue.

    Andrade, Paulina / Narvekar, Parnal / Montoya, Magelda / Michlmayr, Daniela / Balmaseda, Angel / Coloma, Josefina / Harris, Eva

    The Journal of infectious diseases

    2020  Volume 222, Issue 4, Page(s) 590–600

    Abstract: Background: The 4 antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each other and with the closely related Zika flavivirus (ZIKV). The development of polyclonal memory B cells (MBCs) to the 4 DENV serotypes and ZIKV ... ...

    Abstract Background: The 4 antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each other and with the closely related Zika flavivirus (ZIKV). The development of polyclonal memory B cells (MBCs) to the 4 DENV serotypes and ZIKV during DENV infection is not fully understood.
    Methods: In this study, we analyzed polyclonal MBCs at the single-cell level from peripheral blood mononuclear cells collected ~2 weeks or 6-7 months postprimary or postsecondary DENV infection from a pediatric hospital-based study in Nicaragua using a Multi-Color FluoroSpot assay.
    Results: Dengue virus elicits robust type-specific and cross-reactive MBC responses after primary and secondary DENV infection, with a significantly higher cross-reactive response in both. Reactivity to the infecting serotype dominated the total MBC response. Although the frequency and proportion of type-specific and cross-reactive MBCs were comparable between primary and secondary DENV infections, within the cross-reactive response, the breadth of MBC responses against different serotypes was greater after secondary DENV infection. Dengue virus infection also induced cross-reactive MBC responses recognizing ZIKV, particularly after secondary DENV infection.
    Conclusions: Overall, our study sheds light on the polyclonal MBC response to DENV and ZIKV in naive and DENV-preimmune subjects, with important implications for natural infections and vaccine development.
    MeSH term(s) Adolescent ; Antibodies, Viral/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Child ; Child, Preschool ; Cross Reactions/immunology ; Dengue/immunology ; Dengue/virology ; Dengue Virus/immunology ; Enzyme-Linked Immunospot Assay ; Female ; Hospitals, Pediatric ; Host-Pathogen Interactions/immunology ; Humans ; Immunologic Memory ; Infant ; Leukocytes, Mononuclear ; Male ; Nicaragua ; Serogroup ; Zika Virus/immunology ; Zika Virus Infection/immunology ; Zika Virus Infection/virology
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2020-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiaa120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.

    Dias, Antonio G / Atyeo, Caroline / Loos, Carolin / Montoya, Magelda / Roy, Vicky / Bos, Sandra / Narvekar, Parnal / Singh, Tulika / Katzelnick, Leah C / Kuan, Guillermina / Lauffenburger, Douglas A / Balmaseda, Angel / Alter, Galit / Harris, Eva

    Science translational medicine

    2022  Volume 14, Issue 651, Page(s) eabm3151

    Abstract: Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have ... ...

    Abstract Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total immunoglobulin G (IgG), IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.
    MeSH term(s) Antibodies, Viral ; Child ; Coinfection ; Cross Reactions ; Dengue ; Dengue Virus ; Humans ; Immunoglobulin Fc Fragments ; Immunoglobulin G
    Chemical Substances Antibodies, Viral ; Immunoglobulin Fc Fragments ; Immunoglobulin G
    Language English
    Publishing date 2022-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abm3151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine.

    Michlmayr, Daniela / Andrade, Paulina / Nascimento, Eduardo J M / Parker, Allan / Narvekar, Parnal / Dean, Hansi J / Harris, Eva

    The Journal of infectious diseases

    2020  Volume 223, Issue 2, Page(s) 247–257

    Abstract: Background: Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1-4). Takeda's live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 ... ...

    Abstract Background: Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1-4). Takeda's live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 and 4 on the DENV2 backbone. The multicolor FluoroSpot (MCF) assay enables quantitation of serotype-specific and cross-reactive individual memory B cells (MBCs) secreting DENV-specific antibodies in a polyclonal mixture.
    Methods: Using the MCF assay, we determined the type-specific and cross-reactive MBC response in peripheral blood mononuclear cells collected pre- and postvaccination from 7 macaques and 15 randomly selected individuals who received TAK-003 (8 DENV seronegative and 7 DENV seropositive) in a phase 2 clinical trial in Singapore (DEN-205 study).
    Results: Preexisting DENV-specific MBC responses were detected only in seropositive vaccine recipients at day 0. Following vaccination, both type-specific and cross-reactive MBCs to all 4 DENV serotypes were observed in all macaques and clinical trial participants. The proportion of type-specific MBCs was higher than cross-reactive MBCs and remained stable between day 30 and 360 post vaccination.
    Conclusions: These results demonstrate that, unlike primary or secondary natural DENV infection, tetravalent vaccination elicits tetravalent type-specific MBCs, and thus all 4 components of TAK-003 contribute to the DENV-specific MBC response following vaccination.
    Clinical trials registration: NCT02425098.
    MeSH term(s) Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Antibody Specificity/immunology ; B-Lymphocytes/immunology ; Cross Reactions/immunology ; Dengue/immunology ; Dengue/prevention & control ; Dengue Vaccines/administration & dosage ; Dengue Vaccines/immunology ; Dengue Virus/classification ; Dengue Virus/immunology ; Humans ; Immunologic Memory ; Macaca ; Serogroup ; Singapore ; Vaccination ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Dengue Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2020-06-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiaa346
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  5. Article ; Online: Polygodial analog induces apoptosis in LNCaP prostate cancer cells.

    Dasari, Subramanyam / Samy, Angela Lincy Prem Antony / Narvekar, Parnal / Dontaraju, Venkata Satish / Dasari, Ramesh / Kornienko, Alexander / Munirathinam, Gnanasekar

    European journal of pharmacology

    2018  Volume 828, Page(s) 154–162

    Abstract: Prostate cancer (PCa) is the second leading cause of death in American men. The chemotherapeutic treatment strategies are generally not effective and can lead to side effects. Hence, there is an urgent need to identify novel chemotherapeutic agents. The ... ...

    Abstract Prostate cancer (PCa) is the second leading cause of death in American men. The chemotherapeutic treatment strategies are generally not effective and can lead to side effects. Hence, there is an urgent need to identify novel chemotherapeutic agents. The aim of this study was to synthesize and evaluate the therapeutic effects of a synthetic analog of polygodial (PG), a pungent constituent abundantly present in mountain pepper, water pepper and dorrigo pepper, on LNCaP PCa cell line and its anti-cancer mechanisms in a preclinical study. We evaluated the anti-cancer potential of the PG analog namely DRP-27 using various assays such as cell viability by MTT assay, anchorage independent growth by soft agar assay, reactive oxygen species generation by 2',7'-dichlorofluorescein probe-based fluorescence assay, and apoptosis by Annexin-V and TUNEL assays respectively. Western blot analysis was performed to identify the molecular mechanism of DRP-27-induced cell death. Our results showed that DRP-27 significantly inhibited LNCaP cell proliferation in a dose-dependent manner at 48 h treatment in vitro. In addition, DRP-27 potently inhibited anchorage-independent growth of these cells. Flow cytometry, Annexin-V and TUNEL assays confirmed that DRP-27 induces apoptosis in LNCaP cells. DRP-27 also induced the activation of intracellular reactive oxygen species. Western blot analysis revealed that DRP-27 downregulated the expression of survivin, while activating Bax and DNA damage marker pH
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Damage ; Enzyme Activation/drug effects ; Humans ; Male ; Prostatic Neoplasms/pathology ; Reactive Oxygen Species/metabolism ; Sesquiterpenes/chemistry ; Sesquiterpenes/pharmacology
    Chemical Substances Antineoplastic Agents ; Reactive Oxygen Species ; Sesquiterpenes ; polygodial (5FAF7T66M7) ; Caspase 3 (EC 3.4.22.-)
    Language English
    Publishing date 2018-03-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2018.03.029
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  6. Article: Antioxidant Activity of Yichun Blue Honeysuckle (YBHS) Berry Counteracts CCl₄-Induced Toxicity in Liver Injury Model of Mice.

    Wang, Mian-Ying / Srinivasan, Madhuwanti / Dasari, Subramanyam / Narvekar, Parnal / Samy, Angela Lincy Prem Antony / Dontaraju, Venkata Satish / Peng, Lin / Anderson, Gary L / Munirathinam, Gnanasekar

    Antioxidants (Basel, Switzerland)

    2017  Volume 6, Issue 3

    Abstract: Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine ... ...

    Abstract Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine how it provides protection against oxidative stress. Eight-week old mice (25 male and 25 female) were randomized into five groups (
    Language English
    Publishing date 2017-06-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox6030050
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