Dataset Information

Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections.

ABSTRACT:

Background

Monoclonal antibody therapy has an important role to play as a post-exposure prophylactic and therapeutic for the treatment of viral infections, including emerging infections. For example, several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp, a cocktail of three monoclonal antibodies which are expressed in Nicotiana benthamiana.

Discussion

The majority of monoclonal antibodies in clinical use are expressed in mammalian cell lines which offer native folding and glycosylation of the expressed antibody. Monoclonal antibody expression in vegetal systems offers advantages over expression in mammalian cell lines, including improved potential for scale up and reduced costs. In this paper, I highlight the advantages of an upcoming protozoal system for the expression of recombinant antibody formats. Leishmania tarentolae offers a robust, economical expression of proteins with mammalian glycosylation patterns expressed in stable cell lines and grown in suspension culture. Several advantages of this system make it particularly suited for use in developing contexts.

Summary

Given the potential importance of monoclonal antibody therapy in the containment of emerging viral infections, novel and alternative strategies to improve production must be explored.

SUBMITTER: Jones JD

PROVIDER: S-EPMC4506428 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections.

Jones Joshua D JD

Infectious diseases of poverty 20150401

<h4>Background</h4>Monoclonal antibody therapy has an important role to play as a post-exposure prophylactic and therapeutic for the treatment of viral infections, including emerging infections. For example, several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp, a cocktail of three monoclonal antibodies which are expressed in Nicotiana benthamiana.<h4>Discussion</h4>The majority of monoclonal antibodies in clinical use are expressed in mammalian cell lines w ...[more]

PMID: 26191408

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Project description:The genomic DNAs of strains JPCM5 and 263 of L. infantum, strains LV39 and Friedlin of L. major and strains Parrot-TarII and S125 of L. tarentolae were used in comparative genomic hybridizations to reveal the intra-species and inter-species gene content, and to validate L. tarentolae Parrot-TarII genome sequencing results. Leishmania (Sauroleishmania) tarentolae was first isolated in the lizard Tarentola mauritanica. This species is not known to be pathogenic to humans but is often used as a model organism for molecular analyses or protein overproduction. The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved by high-throughput sequencing technologies. The L. tarentolae genome was first assembled de novo and then aligned against the reference L. major Friedlin genome to facilitate contig positioning and annotation, providing a 23-fold coverage of the genome. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described, and it provides an opportunity for comparison with the completed genomes of the pathogenic Leishmania species. A high synteny was observed in de novo assembled contigs between all sequenced Leishmania species. A number of limited chromosomal regions diverged between L. tarentolae and L. infantum, while remaining syntenic with L. major. Globally, over 90% of the L. tarentolae gene content was shared with the other Leishmania species. There were 250 L. major genes absent from L. tarentolae, and interestingly these missing genes were primarily expressed in the intracellular amastigote stage of the pathogenic parasites. This implies that L. tarentolae may have impaired ability to survive as an intracellular parasite. In contrast to other Leishmania genomes, two gene families were expanded in L. tarentolae, namely the leishmanolysin (GP63) and a gene related to the promastigote surface antigen (PSA31C). Overall, L. tarentolae appears to have a gene content more adapted to the insect stage rather than the mammalian one. This may partly explain its inability to replicate within mammalian macrophages and its suspected preferred life style as promastigote in the lizards.

Dataset Information

Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections.

Background

Discussion

Summary

Publications

Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections.

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