期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06741-w
关键词
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资金
- NIH [R01 AI105204]
- Jefferson Vaccine Center
- Fundacao para a Ciencia e Tecnologia (FCT) scholarship [PD/BD/105847/2014]
- NIAID Division of Intramural Research, Battelle Memorial Institute
- NIAID Division of Clinical Research, Battelle Memorial Institute
- U.S. National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I]
- Fundação para a Ciência e a Tecnologia [PD/BD/105847/2014] Funding Source: FCT
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.
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