Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins

Jose A. Quiroz, Ryan J. Malonis, Larissa B. Thackray, Courtney A. Cohen, Jesper Pallesen, Rohit K. Jangra, Rebecca S. Brown, Daniel Hofmann, Frederick W. Holtsberg, Sergey Shulenin, Elisabeth K. Nyakatura, Lorellin A. Durnell, Vinayak Rayannavar, Johanna P. Daily, Andrew B. Ward, M. Javad Aman, John M. Dye, Kartik Chandran, Michael S. Diamond, Margaret KielianJonathan R. Lai

Research output: Contribution to journalArticle

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)e1008061
JournalPLoS pathogens
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2019

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Chikungunya virus
Epitopes
Glycoproteins
Monoclonal Antibodies
Dominican Republic
Alphavirus
Culicidae
Arthritis
Antibody Formation
B-Lymphocytes
Mutation

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins. / Quiroz, Jose A.; Malonis, Ryan J.; Thackray, Larissa B.; Cohen, Courtney A.; Pallesen, Jesper; Jangra, Rohit K.; Brown, Rebecca S.; Hofmann, Daniel; Holtsberg, Frederick W.; Shulenin, Sergey; Nyakatura, Elisabeth K.; Durnell, Lorellin A.; Rayannavar, Vinayak; Daily, Johanna P.; Ward, Andrew B.; Aman, M. Javad; Dye, John M.; Chandran, Kartik; Diamond, Michael S.; Kielian, Margaret; Lai, Jonathan R.

In: PLoS pathogens, Vol. 15, No. 11, 01.11.2019, p. e1008061.

Research output: Contribution to journalArticle

Quiroz, JA, Malonis, RJ, Thackray, LB, Cohen, CA, Pallesen, J, Jangra, RK, Brown, RS, Hofmann, D, Holtsberg, FW, Shulenin, S, Nyakatura, EK, Durnell, LA, Rayannavar, V, Daily, JP, Ward, AB, Aman, MJ, Dye, JM, Chandran, K, Diamond, MS, Kielian, M & Lai, JR 2019, 'Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins', PLoS pathogens, vol. 15, no. 11, pp. e1008061. https://doi.org/10.1371/journal.ppat.1008061
Quiroz, Jose A. ; Malonis, Ryan J. ; Thackray, Larissa B. ; Cohen, Courtney A. ; Pallesen, Jesper ; Jangra, Rohit K. ; Brown, Rebecca S. ; Hofmann, Daniel ; Holtsberg, Frederick W. ; Shulenin, Sergey ; Nyakatura, Elisabeth K. ; Durnell, Lorellin A. ; Rayannavar, Vinayak ; Daily, Johanna P. ; Ward, Andrew B. ; Aman, M. Javad ; Dye, John M. ; Chandran, Kartik ; Diamond, Michael S. ; Kielian, Margaret ; Lai, Jonathan R. / Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins. In: PLoS pathogens. 2019 ; Vol. 15, No. 11. pp. e1008061.
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