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Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever
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Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever
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Journal Article
Non-neutralizing antibodies elicited by recombinant Lassa–Rabies vaccine are critical for protection against Lassa fever
2018
Overview
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.
There is currently no approved vaccine for Lassa fever virus (LASV). Here, Abreu-Mota et al. develop an inactivated, adjuvanted vaccine candidate expressing LASV glycoprotein (GPC) in a rabies virus vector, and show that non-neutralizing LASV GPC-specific antibodies are a major mechanism of protection.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 64/60
/ 82/1
/ 82/51
/ 82/80
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Antibody-Dependent Cell Cytotoxicity - immunology
/ Fever
/ Genetic Vectors - metabolism
/ Humanities and Social Sciences
/ Immunoglobulin G - metabolism
/ Lassa Fever - prevention & control
/ Lipid A
/ Mice
/ Rabies
/ Rabies Vaccines - immunology
/ Science
/ Vaccines
/ Vaccines, Synthetic - immunology
/ Viruses
