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TitleCrimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.
Journal, issue, pagesCell Rep, Vol. 43, Issue 7, Page 114502, Year 2024
Publish dateJul 23, 2024
AuthorsOlivia 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 /
PubMed AbstractCrimean-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 ...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.
External linksCell Rep / PubMed:39002130 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.8 - 5.6 Å
Structure data

EMDB-43551: CCHFV GP38 bound with ADI-46143 and ADI-46158 Fabs
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-43552: CCHFV GP38 bound with ADI-58062 and ADI-63530 Fabs
Method: EM (single particle) / Resolution: 5.1 Å

EMDB-43553: CCHFV GP38 bound with ADI-58026 and ADI-63547 Fabs
Method: EM (single particle) / Resolution: 4.9 Å

43604

8vww

EMDB-43604, PDB-8vww:
CCHFV GP38 bound to ADI-46152 and ADI-58048 Fabs
Method: EM (single particle) / Resolution: 3.9 Å

PDB-8vvk:
CCHFV GP38 bound to ADI-46143 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.61 Å

PDB-8vvl:
CCHFV GP38 bound to c13G8 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.8 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-SO4:
SULFATE ION

ChemComp-CL:
Unknown entry

ChemComp-CO:
Unknown entry

Source
  • homo sapiens (human)
  • crimean-congo hemorrhagic fever virus
  • crimean-congo hemorrhagic fever virus strain ibar10200
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / CCHFV / GP38 / Antibody / Immunology / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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