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  1. Article ; Online: Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype

    Sandra Bos / Aaron L. Graber / Jaime A. Cardona-Ospina / Elias M. Duarte / Jose Victor Zambrana / Jorge A. Ruíz Salinas / Reinaldo Mercado-Hernandez / Tulika Singh / Leah C. Katzelnick / Aravinda de Silva / Guillermina Kuan / Angel Balmaseda / Eva Harris

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 13

    Abstract: Abstract Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are ...

    Abstract Abstract Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Favipiravir (T-705) Protects IFNAR −/− Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner

    Keesha Matz / Jackson Emanuel / Julie Callison / Don Gardner / Rebecca Rosenke / Reinaldo Mercado-Hernandez / Brandi N. Williamson / Heinz Feldmann / Andrea Marzi

    Microorganisms, Vol 9, Iss 1178, p

    2021  Volume 1178

    Abstract: Zika virus (ZIKV), a member of the Flaviviridae family, is an important human pathogen that has caused epidemics in Africa, Southeast Asia, and the Americas. No licensed treatments for ZIKV disease are currently available. Favipiravir (T-705; 6-fluoro-3- ... ...

    Abstract Zika virus (ZIKV), a member of the Flaviviridae family, is an important human pathogen that has caused epidemics in Africa, Southeast Asia, and the Americas. No licensed treatments for ZIKV disease are currently available. Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and ribavirin (1-(β-D-Ribofuranosyl)-1 H -1,2,4-triazole-3-carboxamide) are nucleoside analogs that have exhibited antiviral activity against a broad spectrum of RNA viruses, including some flaviviruses. In this study, we strengthened evidence for favipiravir and ribavirin inhibition of ZIKV replication in vitro. Testing in IFNAR −/− mice revealed that daily treatments of favipiravir were sufficient to provide protection against lethal ZIKV challenge in a dose-dependent manner but did not completely abrogate disease. Ribavirin, on the other hand, had no beneficial effect against ZIKV infection in this model and under the conditions examined. Combined treatment of ribavirin and favipiravir did not show improved outcomes over ribavirin alone. Surprisingly, outcome of favipiravir treatment was sex-dependent, with 87% of female but only 25% of male mice surviving lethal ZIKV infection. Since virus mutations were not associated with outcome, a sex-specific host response likely explains the observed sex difference.
    Keywords flavivirus ; ZIKV ; mouse model ; sex bias ; ribavirin ; antiviral ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge

    Andrea Marzi / Pierce Reynolds / Reinaldo Mercado-Hernandez / Julie Callison / Friederike Feldmann / Rebecca Rosenke / Tina Thomas / Dana P. Scott / Patrick W. Hanley / Elaine Haddock / Heinz Feldmann

    EBioMedicine, Vol 49, Iss , Pp 223-

    2019  Volume 231

    Abstract: Summary: Background: Ebola virus (EBOV), variant Makona, was the causative agent of the 2013–2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several ... ...

    Abstract Summary: Background: Ebola virus (EBOV), variant Makona, was the causative agent of the 2013–2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen. Methods: Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge. Findings: We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 107 to 1 × 101 plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. Interpretation: Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability - two critical concerns in public health response. Funding: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Keywords: Ebola virus, EBOV-Makona, Macaque model, VSV-EBOV, Low-dose vaccination
    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Subject code 630
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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