8VWW

CCHFV GP38 bound to ADI-46152 and ADI-58048 Fabs

Summary for 8VWW

• Entry DOI: 10.2210/pdb8vww/pdb
• EMDB information: 43604
• Descriptor: GP38, ADI-46152 Fab Heavy Chain, ADI-46152 Fab Light Chain, ... (5 entities in total)
• Functional Keywords: cchfv, gp38, antibody, immunology, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Crimean-Congo hemorrhagic fever virus strain IbAr10200; More
• Total number of polymer chains: 5
• Total formula weight: 124726.16

Authors

Hjorth, C.K.,McLellan, J.S. (deposition date: 2024-02-02, release date: 2024-07-24, Last modification date: 2024-11-06)

Primary citation

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.,Lobel, L.,Zeitlin, L.,Walker, L.M.,Dye, J.M.,Chandran, K.,Herbert, A.S.,Pauli, N.T.,McLellan, J.S.
Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.
Cell Rep, 43:114502-114502, 2024

PubMed 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.

PubMed: 39002130
DOI: 10.1016/j.celrep.2024.114502

Experimental method

ELECTRON MICROSCOPY (3.9 Å)