A combination of two resistance mechanisms is critical for
tick-borne encephalitis virus escape from a broadly
neutralizing human antibody

J 2023

A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody

SVOBODA, Pavel, Jan HAVIERNIK, Petr BEDNÁŘ, Milos MATKOVIC, Tomas Cervantes RINCO et. al.

Basic information

Original name

A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody

Authors

SVOBODA, Pavel (203 Czech Republic, belonging to the institution), Jan HAVIERNIK (203 Czech Republic, belonging to the institution), Petr BEDNÁŘ (203 Czech Republic, belonging to the institution), Milos MATKOVIC, Tomas Cervantes RINCO, Jennifer KEEFFE, Martin PALUS, Jiri SALAT, Marianna AGUDELO, Michel C NUSSENZWEIG, Andrea CAVALLI, Davide F ROBBIANI and Daniel RŮŽEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cell Reports, Elsevier Inc. 2023, 2211-1247

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.800 in 2022

RIV identification code

RIV/00216224:14310/23:00132673

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.celrep.2023.113149

UT WoS

001101035500001

Keywords in English

tick-borne encephalitis; tick-borne encephalitis virus; monoclonal antibody; escape mutant; neutralization

Abstract

V originále

Tick-borne encephalitis virus (TBEV) is a flavivirus that causes human neuroinfections and represents a growing health problem. The human monoclonal antibody T025 targets envelope protein domain III (EDIII) of TBEV and related tick-borne flaviviruses, potently neutralizing TBEV in vitro and in preclinical models, representing a promising candidate for clinical development. We demonstrate that TBEV escape in the presence of T025 or T028 (another EDIII-targeting human monoclonal antibody) results in virus variants of reduced pathogenicity, characterized by distinct sets of amino acid changes in EDII and EDIII that are jointly needed to confer resistance. EDIII substitution K311N impairs formation of a salt bridge critical for T025-epitope interaction. EDII substitution E230K is not on the T025 epitope but likely induces quaternary rearrangements of the virus surface because of repulsion of positively charged residues on the adjacent EDI. A combination of T025 and T028 prevents virus escape and improves neutralization.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

SVOBODA, Pavel, Jan HAVIERNIK, Petr BEDNÁŘ, Milos MATKOVIC, Tomas Cervantes RINCO, Jennifer KEEFFE, Martin PALUS, Jiri SALAT, Marianna AGUDELO, Michel C NUSSENZWEIG, Andrea CAVALLI, Davide F ROBBIANI and Daniel RŮŽEK. A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody. Cell Reports. Elsevier Inc., 2023, vol. 42, No 9, p. 1-16. ISSN 2211-1247. Available from: https://dx.doi.org/10.1016/j.celrep.2023.113149.

@article{2353807,
   author = {Svoboda, Pavel and Haviernik, Jan and Bednář, Petr and Matkovic, Milos and Rinco, Tomas Cervantes and Keeffe, Jennifer and Palus, Martin and Salat, Jiri and Agudelo, Marianna and Nussenzweig, Michel C and Cavalli, Andrea and Robbiani, Davide F and Růžek, Daniel},
   article_number = {9},
   doi = {http://dx.doi.org/10.1016/j.celrep.2023.113149},
   keywords = {tick-borne encephalitis; tick-borne encephalitis virus; monoclonal antibody; escape mutant; neutralization},
   language = {eng},
   issn = {2211-1247},
   journal = {Cell Reports},
   title = {A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody},
   url = {https://doi.org/10.1016/j.celrep.2023.113149},
   volume = {42},
   year = {2023}
}

TY  - JOUR
ID  - 2353807
AU  - Svoboda, Pavel - Haviernik, Jan - Bednář, Petr - Matkovic, Milos - Rinco, Tomas Cervantes - Keeffe, Jennifer - Palus, Martin - Salat, Jiri - Agudelo, Marianna - Nussenzweig, Michel C - Cavalli, Andrea - Robbiani, Davide F - Růžek, Daniel
PY  - 2023
TI  - A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody
JF  - Cell Reports
VL  - 42
IS  - 9
SP  - 1-16
EP  - 1-16
PB  - Elsevier Inc.
SN  - 22111247
KW  - tick-borne encephalitis
KW  - tick-borne encephalitis virus
KW  - monoclonal antibody
KW  - escape mutant
KW  - neutralization
UR  - https://doi.org/10.1016/j.celrep.2023.113149
N2  - Tick-borne encephalitis virus (TBEV) is a flavivirus that causes human neuroinfections and represents a growing health problem. The human monoclonal antibody T025 targets envelope protein domain III (EDIII) of TBEV and related tick-borne flaviviruses, potently neutralizing TBEV in vitro and in preclinical models, representing a promising candidate for clinical development. We demonstrate that TBEV escape in the presence of T025 or T028 (another EDIII-targeting human monoclonal antibody) results in virus variants of reduced pathogenicity, characterized by distinct sets of amino acid changes in EDII and EDIII that are jointly needed to confer resistance. EDIII substitution K311N impairs formation of a salt bridge critical for T025-epitope interaction. EDII substitution E230K is not on the T025 epitope but likely induces quaternary rearrangements of the virus surface because of repulsion of positively charged residues on the adjacent EDI. A combination of T025 and T028 prevents virus escape and improves neutralization.
ER  -

SVOBODA, Pavel, Jan HAVIERNIK, Petr BEDNÁŘ, Milos MATKOVIC, Tomas Cervantes RINCO, Jennifer KEEFFE, Martin PALUS, Jiri SALAT, Marianna AGUDELO, Michel C NUSSENZWEIG, Andrea CAVALLI, Davide F ROBBIANI and Daniel RŮŽEK. A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody. \textit{Cell Reports}. Elsevier Inc., 2023, vol.~42, No~9, p.~1-16. ISSN~2211-1247. Available from: https://dx.doi.org/10.1016/j.celrep.2023.113149.

Detailed Information on Publication Record