Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Robert W. Cross, Aliza Borenstein-Katz, Mathieu Mateo, Sylvain Baize, Vered Padler-Karavani, Thomas W. Geisbert, Ron Diskin

Research output: Contribution to journalArticle

Abstract

Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens.

Original languageEnglish (US)
Article number67
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

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Arenavirus
Tropics
Transferrin Receptors
Viruses
tropical regions
Immunotherapy
Biological Warfare Agents
viruses
Pathogens
biological weapons
Neutralizing Antibodies
fever
rodents
Glycoproteins
combat
countermeasures
pathogens
antibodies
Molecules
South America

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Cohen-Dvashi, H., Amon, R., Agans, K. N., Cross, R. W., Borenstein-Katz, A., Mateo, M., ... Diskin, R. (2020). Rational design of universal immunotherapy for TfR1-tropic arenaviruses. Nature communications, 11(1), [67]. https://doi.org/10.1038/s41467-019-13924-6

Rational design of universal immunotherapy for TfR1-tropic arenaviruses. / Cohen-Dvashi, Hadas; Amon, Ron; Agans, Krystle N.; Cross, Robert W.; Borenstein-Katz, Aliza; Mateo, Mathieu; Baize, Sylvain; Padler-Karavani, Vered; Geisbert, Thomas W.; Diskin, Ron.

In: Nature communications, Vol. 11, No. 1, 67, 01.12.2020.

Research output: Contribution to journalArticle

Cohen-Dvashi, H, Amon, R, Agans, KN, Cross, RW, Borenstein-Katz, A, Mateo, M, Baize, S, Padler-Karavani, V, Geisbert, TW & Diskin, R 2020, 'Rational design of universal immunotherapy for TfR1-tropic arenaviruses', Nature communications, vol. 11, no. 1, 67. https://doi.org/10.1038/s41467-019-13924-6
Cohen-Dvashi, Hadas ; Amon, Ron ; Agans, Krystle N. ; Cross, Robert W. ; Borenstein-Katz, Aliza ; Mateo, Mathieu ; Baize, Sylvain ; Padler-Karavani, Vered ; Geisbert, Thomas W. ; Diskin, Ron. / Rational design of universal immunotherapy for TfR1-tropic arenaviruses. In: Nature communications. 2020 ; Vol. 11, No. 1.
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