A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses

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...

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Published in:Journal of virology Vol. 79; no. 22; p. 13934
Main Authors: Lukashevich, Igor S, Patterson, Jean, Carrion, Ricardo, Moshkoff, Dmitry, Ticer, Anysha, Zapata, Juan, Brasky, Kathleen, Geiger, Robert, Hubbard, Gene B, Bryant, Joseph, Salvato, Maria S
Format: Journal Article
Language:English
Published: United States 01.11.2005
Subjects:
Adoptive Transfer
Animals
Body Weight
Disease Models, Animal
Guinea Pigs
Lassa Fever - immunology
Lassa Fever - pathology
Lassa virus - genetics
Lassa virus - immunology
Liver - immunology
Liver - pathology
Liver - virology
Lung - immunology
Lung - pathology
Lung - virology
Mice
Mice, Inbred CBA
RNA, Viral - genetics
Spleen - immunology
Vaccines, Attenuated
Viral Load
Viral Vaccines
ISSN:0022-538X
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Abstract 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.
AbstractList 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.
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.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.
Author Patterson, Jean
Salvato, Maria S
Lukashevich, Igor S
Ticer, Anysha
Geiger, Robert
Zapata, Juan
Hubbard, Gene B
Bryant, Joseph
Moshkoff, Dmitry
Carrion, Ricardo
Brasky, Kathleen
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  surname: Lukashevich
  fullname: Lukashevich, Igor S
  email: lukashev@umbi.umd.edu
  organization: Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA. lukashev@umbi.umd.edu
– sequence: 2
  givenname: Jean
  surname: Patterson
  fullname: Patterson, Jean
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  givenname: Ricardo
  surname: Carrion
  fullname: Carrion, Ricardo
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  givenname: Dmitry
  surname: Moshkoff
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  surname: Ticer
  fullname: Ticer, Anysha
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  givenname: Joseph
  surname: Bryant
  fullname: Bryant, Joseph
– sequence: 11
  givenname: Maria S
  surname: Salvato
  fullname: Salvato, Maria S
BackLink https://www.ncbi.nlm.nih.gov/pubmed/16254329$$D View this record in MEDLINE/PubMed
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SubjectTerms Adoptive Transfer
Animals
Body Weight
Disease Models, Animal
Guinea Pigs
Lassa Fever - immunology
Lassa Fever - pathology
Lassa virus - genetics
Lassa virus - immunology
Liver - immunology
Liver - pathology
Liver - virology
Lung - immunology
Lung - pathology
Lung - virology
Mice
Mice, Inbred CBA
RNA, Viral - genetics
Spleen - immunology
Vaccines, Attenuated
Viral Load
Viral Vaccines
Title A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses
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