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Journal of Virology, November 2005, p. 13934-13942, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13934-13942.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Live Attenuated Vaccine for Lassa Fever Made by Reassortment of Lassa and Mopeia Viruses

Igor S. Lukashevich,1* Jean Patterson,2 Ricardo Carrion,2 Dmitry Moshkoff,1 Anysha Ticer,2 Juan Zapata,1 Kathleen Brasky,2 Robert Geiger,2 Gene B. Hubbard,2 Joseph Bryant,1 and Maria S. Salvato1

Institute of Human Virology, Baltimore, Maryland,1 Southwest Foundation for Biomedical Research, San Antonio, Texas2

Received 2 August 2005/ Accepted 18 August 2005

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 LASV 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.

* Corresponding author. Mailing address: Institute of Human Virology (IHV), University of Maryland Biotechnology Institute (UMBI), 725 West Lombard Street, Baltimore, MD 21201. Phone: (410) 706-1366. Fax: (410) 706-5198. E-mail: lukashev{at}umbi.umd.edu.

Journal of Virology, November 2005, p. 13934-13942, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13934-13942.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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