title: Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.
abstract: Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Dalebout
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bredenbeek
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carrion
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brasky
authors.forename: Jean
authors.initials: J
authors.lastname: Patterson
authors.forename: Marco
authors.initials: M
authors.lastname: Goicochea
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryant
authors.forename: Maria S
authors.initials: MS
authors.lastname: Salvato
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006168:Guinea Pigs; D007835:Lassa Fever / Q000517:prevention & control*; D051379:Mice; D008808:Mice, Inbred CBA; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D022341:Yellow Fever Vaccine / Q000235:genetics* / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D022341:Yellow Fever Vaccine; C066508:glycoprotein gp1, lassa virus; C077198:glycoprotein gp2, lassa virus