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Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Abstract : Certain arenaviruses that circulate in rodent populations can cause life-threatening hemor-rhagic 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 immu-noadhesins and can be used to combat other zoonotic pathogens.
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Submitted on : Friday, February 28, 2020 - 4:22:40 PM
Last modification on : Saturday, September 24, 2022 - 3:10:05 PM
Long-term archiving on: : Friday, May 29, 2020 - 5:27:09 PM


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Hadas Cohen-Dvashi, Ron Amon, Krystle N Agans, Robert W Cross, Aliza Borenstein-Katz, et al.. Rational design of universal immunotherapy for TfR1-tropic arenaviruses. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.67. ⟨10.1038/s41467-019-13924-6⟩. ⟨inserm-02494370⟩



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