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

Nat Commun. 2018 Oct 11;9(1):4223. doi: 10.1038/s41467-018-06741-w.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Cell Membrane / metabolism
  • Genetic Vectors / metabolism
  • Glucosides
  • Glycoproteins / metabolism
  • Guinea Pigs
  • Immunity, Humoral
  • Immunization
  • Immunoglobulin G / metabolism
  • Lassa Fever / immunology*
  • Lassa Fever / prevention & control*
  • Lassa Fever / virology
  • Lassa virus / immunology*
  • Lassa virus / pathogenicity
  • Lipid A
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Rabies Vaccines / immunology*
  • Receptors, IgG / metabolism
  • Vaccines, Synthetic / immunology*
  • Virion / metabolism
  • Virulence


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Glucosides
  • Glycoproteins
  • Immunoglobulin G
  • Lipid A
  • Rabies Vaccines
  • Receptors, IgG
  • Vaccines, Synthetic
  • glucopyranosyl lipid-A