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 and Ron Diskin ()
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Hadas Cohen-Dvashi: Weizmann Institute of Science
Ron Amon: Tel Aviv University
Krystle N. Agans: University of Texas Medical Branch
Robert W. Cross: University of Texas Medical Branch
Aliza Borenstein-Katz: Weizmann Institute of Science
Mathieu Mateo: Centre International de Recherche en Infectiologie (INSERM, CNRS, ENS Lyon, Université Lyon I)
Sylvain Baize: Centre International de Recherche en Infectiologie (INSERM, CNRS, ENS Lyon, Université Lyon I)
Vered Padler-Karavani: Tel Aviv University
Thomas W. Geisbert: University of Texas Medical Branch
Ron Diskin: Weizmann Institute of Science

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13924-6

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