Clark, LarsMahmutovic, SelmaRaymond, Donald D.Dilanyan, TaleenKoma, TakaakiManning, John T.Shankar, SundareshLevis, Silvana C.Briggiler, Ana M.Enria, Delia A.Wucherpfennig, KaiPaessler, SlobodanAbraham, Jonathan2018-06-272018Clark, L. E., S. Mahmutovic, D. D. Raymond, T. Dilanyan, T. Koma, J. T. Manning, S. Shankar, et al. 2018. “Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.” Nature Communications 9 (1): 1884. doi:10.1038/s41467-018-04271-z. http://dx.doi.org/10.1038/s41467-018-04271-z.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160362While 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.en-USJournal Article2018-06-2710.1038/s41467-018-04271-z