Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38

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

doi:10.1016/j.celrep.2024.114502

Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38

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

The Shraga Segal Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English
Article number	114502
Journal	Cell Reports
Volume	43
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2024.114502
State	Published - 23 Jul 2024

Keywords

CCHFV
CP: Immunology
Crimean-Congo hemorrhagic fever virus
GP38
Nairoviridae
antibody therapeutics
human monoclonal antibody
tickborne
viral glycoprotein

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2024.114502

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Shin, O. S., Monticelli, S. R., Hjorth, C. K., Hornet, V., Doyle, M., Abelson, D., Kuehne, A. I., Wang, A., Bakken, R. R., Mishra, A. K., Middlecamp, M., Champney, E., Stuart, L., Maurer, D. P., Li, J., Berrigan, J., Barajas, J., Balinandi, S., Lutwama, J. J., ... McLellan, J. S. (2024). Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38. Cell Reports, 43(7), Article 114502. https://doi.org/10.1016/j.celrep.2024.114502

@article{3e021ed3ce2f4d978f493f56581b869c,

title = "Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38",

abstract = "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.",

keywords = "CCHFV, CP: Immunology, Crimean-Congo hemorrhagic fever virus, GP38, Nairoviridae, antibody therapeutics, human monoclonal antibody, tickborne, viral glycoprotein",

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

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jul,

day = "23",

doi = "10.1016/j.celrep.2024.114502",

language = "English",

volume = "43",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

}

Shin, OS, Monticelli, SR, Hjorth, CK, Hornet, V, Doyle, M, Abelson, D, Kuehne, AI, Wang, A, Bakken, RR, Mishra, AK, Middlecamp, M, Champney, E, Stuart, L, Maurer, DP, Li, J, Berrigan, J, Barajas, J, Balinandi, S, Lutwama, JJ, Lobel, L, Zeitlin, L, Walker, LM, Dye, JM, Chandran, K, Herbert, AS, Pauli, NT & McLellan, JS 2024, 'Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38', Cell Reports, vol. 43, no. 7, 114502. https://doi.org/10.1016/j.celrep.2024.114502

TY - JOUR

T1 - Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38

AU - Shin, Olivia S.

AU - Monticelli, Stephanie R.

AU - Hjorth, Christy K.

AU - Hornet, Vladlena

AU - Doyle, Michael

AU - Abelson, Dafna

AU - Kuehne, Ana I.

AU - Wang, Albert

AU - Bakken, Russell R.

AU - Mishra, Akaash K.

AU - Middlecamp, Marissa

AU - Champney, Elizabeth

AU - Stuart, Lauran

AU - Maurer, Daniel P.

AU - Li, Jiannan

AU - Berrigan, Jacob

AU - Barajas, Jennifer

AU - Balinandi, Stephen

AU - Lutwama, Julius J.

AU - Lobel, Leslie

AU - Zeitlin, Larry

AU - Walker, Laura M.

AU - Dye, John M.

AU - Chandran, Kartik

AU - Herbert, Andrew S.

AU - Pauli, Noel T.

AU - McLellan, Jason S.

PY - 2024/7/23

Y1 - 2024/7/23

N2 - 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.

AB - 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.

KW - CCHFV

KW - CP: Immunology

KW - Crimean-Congo hemorrhagic fever virus

KW - GP38

KW - Nairoviridae

KW - antibody therapeutics

KW - human monoclonal antibody

KW - tickborne

KW - viral glycoprotein

UR - https://www.scopus.com/pages/publications/85198243918

U2 - 10.1016/j.celrep.2024.114502

DO - 10.1016/j.celrep.2024.114502

M3 - Article

C2 - 39002130

AN - SCOPUS:85198243918

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 114502

ER -

Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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