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Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses

Author

Listed:
  • Lars E. Clark

    (Harvard Medical School)

  • Selma Mahmutovic

    (Harvard Medical School)

  • Donald D. Raymond

    (Harvard Medical School)

  • Taleen Dilanyan

    (Harvard Medical School)

  • Takaaki Koma

    (University of Texas Medical Branch at Galveston)

  • John T. Manning

    (University of Texas Medical Branch at Galveston)

  • Sundaresh Shankar

    (Harvard Medical School)

  • Silvana C. Levis

    (Instituto Nacional de Enfermedades Virales Humanas “Dr. Julio I. Maiztegui”, Monteagudo 251 Pergamino)

  • Ana M. Briggiler

    (Instituto Nacional de Enfermedades Virales Humanas “Dr. Julio I. Maiztegui”, Monteagudo 251 Pergamino)

  • Delia A. Enria

    (Instituto Nacional de Enfermedades Virales Humanas “Dr. Julio I. Maiztegui”, Monteagudo 251 Pergamino)

  • Kai W. Wucherpfennig

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Harvard Medical School)

  • Slobodan Paessler

    (University of Texas Medical Branch at Galveston)

  • Jonathan Abraham

    (Harvard Medical School
    Harvard Medical School
    Brigham and Women’s Hospital)

Abstract

While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1–Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.

Suggested Citation

  • Lars E. Clark & Selma Mahmutovic & Donald D. Raymond & Taleen Dilanyan & Takaaki Koma & John T. Manning & Sundaresh Shankar & Silvana C. Levis & Ana M. Briggiler & Delia A. Enria & Kai W. Wucherpfenni, 2018. "Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04271-z
    DOI: 10.1038/s41467-018-04271-z
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