Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever

Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson and Matthias J. Schnell ()
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Tiago Abreu-Mota: Sidney Kimmel Medical College at Thomas Jefferson University
Katie R. Hagen: National Institutes of Health
Kurt Cooper: National Institutes of Health
Peter B. Jahrling: National Institutes of Health
Gene Tan: Infectious Disease, The J. Craig Venter Institute
Christoph Wirblich: Sidney Kimmel Medical College at Thomas Jefferson University
Reed F. Johnson: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Matthias J. Schnell: Sidney Kimmel Medical College at Thomas Jefferson University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.

Date: 2018
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DOI: 10.1038/s41467-018-06741-w

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