Journal
JOURNAL OF VIROLOGY
Volume 79, Issue 22, Pages 13934-13942Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.22.13934-13942.2005
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Funding
- NIAID NIH HHS [R01 AI052367, R21 AI053619, R21-AI53619, R21-AI52367, R21 AI059247, R01 AI052367-03, R21 AI052367, R21-AI059247] Funding Source: Medline
- PHS HHS [R01-A52367] Funding Source: Medline
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Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. In murine adoptive-transfer experiments, as little as 150 PFU of ML29 induced protective cell-mediated immunity. All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after IASV challenge without either disease signs or histological lesions. Rhesus macaques inoculated with clone ML29 developed primary virus-specific T cells capable of secreting gamma interferon in response to homologous MOP/LAS and heterologous MOPV and lymphocytic choriomeningitis virus. Detailed examination of two rhesus macaques infected with this MOPV/LAS reassortant revealed no histological lesions or disease signs. Thus, ML29 is a promising attenuated vaccine candidate for Lassa fever.
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