Author: Hornet, Vladlena ; Kuehne, Ana I ; Zeitlin, Larry ; Abelson, Dafna ; Pauli, Noel T ; Herbert, Andrew S ; Lutwama, Julius J ; Barajas, Jennifer ; Maurer, Daniel P ; Stuart, Lauran ; Mishra, Akaash K ; Lobel, Leslie ; Shin, Olivia S ; Champney, Elizabeth ; Doyle, Michael ; Bakken, Russell R ; Wang, Albert ; Berrigan, Jacob ; Li, Jiannan ; McLellan, Jason S ; Walker, Laura M ; Dye, John M ; Balinandi, Stephen ; Chandran, Kartik ; Monticelli, Stephanie R ; Middlecamp, Marissa ; Hjorth, Christy K

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics.

31 Mar 2020·Journal of VirologyQ2 · MEDICINE

Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38

Q2 · MEDICINE

Article

Author: Moyer, Crystal L. ; Mishra, Akaash K. ; El Omari, Kamel ; Bornholdt, Zachary A. ; Abelson, Dafna M. ; Deer, Daniel J. ; McLellan, Jason S. ; Wagner, Armin ; Duman, Ramona ; Geisbert, Thomas W. ; Cross, Robert W. ; Dye, John M. ; Chandran, Kartik ; Lutwama, Julius J. ; Lobel, Leslie ; Zeitlin, Larry

Crimean-Congo hemorrhagic fever virus (CCHFV) is a priority pathogen that poses a high risk to public health. Due to the high morbidity and mortality rates associated with CCHFV infection, there is an urgent need to develop medical countermeasures for disease prevention and treatment. CCHFV GP38, a secreted glycoprotein of unknown function unique to the Nairoviridae family, was recently shown to be the target of a protective antibody against CCHFV. Here, we present the crystal structure of GP38, which revealed a novel fold with distant homology to another CCHFV glycoprotein that is suggestive of a gene duplication event. We also demonstrate that antibody 13G8 protects STAT1-knockout mice against heterologous CCHFV challenge using a clinical isolate from regions where CCHFV is endemic. Collectively, these data advance our understanding of GP38 structure and antigenicity and should facilitate future studies investigating its function.

Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38

Author: Hornet, Vladlena ; Monticelli, Stephanie R ; Abelson, Dafna ; Middlecamp, Marissa ; Lutwama, Julius J ; Hjorth, Christy K ; Maurer, Daniel P ; Bakken, Russell R ; Dye, John M ; Kuehne, Ana I ; Lobel, Leslie ; Shin, Olivia S ; Champney, Elizabeth ; Doyle, Michael ; Herbert, Andrew S ; Stuart, Lauran ; Wang, Albert ; Berrigan, Jacob ; Li, Jiannan ; Barajas, Jennifer ; Zeitlin, Larry ; Walker, Laura M ; Pauli, Noel T ; Mishra, Akaash ; Balinandi, Stephen ; Chandran, Kartik ; McLellan, Jason S

SUMMARYCrimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, unique toNairoviridae, is a target of protective antibodies, but extensive mapping of the human antibody response to GP38 has not been previously performed. Here, we isolated 188 GP38-specific antibodies from human survivors of infection. Competition experiments showed that these antibodies bind across five distinct antigenic sites, encompassing eleven overlapping regions. Additionally, we reveal structures of GP38 bound with nine of these antibodies targeting different antigenic sites. Although GP38-specific antibodies were non-neutralizing, several antibodies were found to have protection equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and inform the development of broadly effective CCHFV antibody therapeutics.

100 Deals associated with chimeric 13G8

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hemorrhagic Fever, Crimean	Preclinical	US	University of Georgia	26 Nov 2022
Hemorrhagic Fever, Crimean	Preclinical	US	University of Maryland Baltimore	26 Nov 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

chimeric 13G8

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation