Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

• Published in: Vaccine 2011-02, Vol.29 (6), p.1248-1257
• Main Authors: Jiang, Xiaohong, Dalebout, Tim J, Bredenbeek, Peter J, Carrion, Ricardo, Brasky, Kathleen, Patterson, Jean, Goicochea, Marco, Bryant, Joseph, Salvato, Maria S, Lukashevich, Igor S
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; antigens; Applied microbiology; Arboviroses; Biological and medical sciences; Biomedical research; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; Cloning; Cytokines; Disease Models, Animal; Drug Carriers; Experiments; Female; Fever; Fundamental and applied biological sciences. Psychology; genes; genetic stability; Genetic Vectors; Genomes; Glycoproteins; Guinea Pigs; Human viral diseases; Immune system; immunity; Immunization; Infectious diseases; Lassa Fever; Lassa Fever - prevention & control; Lassa mammarenavirus; Lassa virus; Lymphocytes; Medical sciences; Mice; Mice, Inbred CBA; Microbiology; Miscellaneous; Proteins; Public health; Recombinant vaccines; RNA polymerase; sterilizing; Tropical diseases; Tropical viral diseases; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vector-borne diseases; Viral diseases; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Virology; virus replication; Viruses; Western Africa; Yellow Fever; Yellow Fever Vaccine - genetics; Yellow Fever Vaccine - immunology; Yellow fever virus; YF17D vaccine
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.11.079

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.