Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis.
Identifieur interne : 000585 ( Main/Exploration ); précédent : 000584; suivant : 000586Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis.
Auteurs : J. Madhumathi [Inde] ; P R Prince [Inde] ; D N Rao [Inde] ; A A Karande [Inde] ; M V R. Reddy [Inde] ; P. Kaliraj [Inde]Source :
- Journal of helminthology [ 1475-2697 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antihelminthe (sang), Antigènes d'helminthe (génétique), Antigènes d'helminthe (immunologie), Cartographie épitopique, Déterminants antigéniques des lymphocytes B (génétique), Déterminants antigéniques des lymphocytes B (immunologie), Filariose lymphatique (), Filariose lymphatique (immunologie), Immunoglobuline G (sang), Modèles animaux de maladie humaine, Murinae, Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Résultat thérapeutique, Vaccins synthétiques (administration et posologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie).
- MESH :
- administration et posologie : Vaccins synthétiques.
- génétique : Antigènes d'helminthe, Déterminants antigéniques des lymphocytes B, Protéines recombinantes, Vaccins synthétiques.
- immunologie : Antigènes d'helminthe, Déterminants antigéniques des lymphocytes B, Filariose lymphatique, Protéines recombinantes, Vaccins synthétiques.
- sang : Anticorps antihelminthe, Immunoglobuline G.
- Animaux, Cartographie épitopique, Filariose lymphatique, Modèles animaux de maladie humaine, Murinae, Résultat thérapeutique.
English descriptors
- KwdEn :
- Animals, Antibodies, Helminth (blood), Antigens, Helminth (genetics), Antigens, Helminth (immunology), Disease Models, Animal, Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (prevention & control), Epitope Mapping, Epitopes, B-Lymphocyte (genetics), Epitopes, B-Lymphocyte (immunology), Immunoglobulin G (blood), Murinae, Recombinant Proteins (genetics), Recombinant Proteins (immunology), Treatment Outcome, Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology).
- MESH :
- chemical , administration & dosage : Vaccines, Synthetic.
- chemical , blood : Antibodies, Helminth, Immunoglobulin G.
- chemical , genetics : Antigens, Helminth, Epitopes, B-Lymphocyte, Recombinant Proteins, Vaccines, Synthetic.
- chemical , immunology : Antigens, Helminth, Epitopes, B-Lymphocyte, Recombinant Proteins, Vaccines, Synthetic.
- immunology : Elephantiasis, Filarial.
- prevention & control : Elephantiasis, Filarial.
- Animals, Disease Models, Animal, Epitope Mapping, Murinae, Treatment Outcome.
Abstract
Human lymphatic filariasis is a neglected tropical disease, causing permanent and long-term disability with severe immunopathology. Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model of Brugia malayi ALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a 'knottin' fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1-30 and 89-128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model, Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections.
DOI: 10.1017/S0022149X16000055
PubMed: 26892175
Affiliations:
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Madhumathi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology,Indian Institute of Technology,Chennai-600036,India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology,Indian Institute of Technology,Chennai-600036</wicri:regionArea><wicri:noRegion>Chennai-600036</wicri:noRegion></affiliation></author><author><name sortKey="Prince, P R" sort="Prince, P R" uniqKey="Prince P" first="P R" last="Prince">P R Prince</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Centre for Biotechnology, Anna University,Chennai600025</wicri:regionArea><wicri:noRegion>Chennai600025</wicri:noRegion></affiliation></author><author><name sortKey="Rao, D N" sort="Rao, D N" uniqKey="Rao D" first="D N" last="Rao">D N Rao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry,All India Institute of Medical Sciences,New Delhi110029,India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biochemistry,All India Institute of Medical Sciences,New Delhi110029</wicri:regionArea><wicri:noRegion>New Delhi110029</wicri:noRegion></affiliation></author><author><name sortKey="Karande, A A" sort="Karande, A A" uniqKey="Karande A" first="A A" last="Karande">A A Karande</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry,Mahatma Gandhi Institute of Medical Sciences,Sevagram442102,India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biochemistry,Mahatma Gandhi Institute of Medical Sciences,Sevagram442102</wicri:regionArea><wicri:noRegion>Sevagram442102</wicri:noRegion></affiliation></author><author><name sortKey="Reddy, M V R" sort="Reddy, M V R" uniqKey="Reddy M" first="M V R" last="Reddy">M V R. 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Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model of Brugia malayi ALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a 'knottin' fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1-30 and 89-128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model, Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections.</div></front></TEI><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Madhumathi, J" sort="Madhumathi, J" uniqKey="Madhumathi J" first="J" last="Madhumathi">J. Madhumathi</name></noRegion><name sortKey="Kaliraj, P" sort="Kaliraj, P" uniqKey="Kaliraj P" first="P" last="Kaliraj">P. Kaliraj</name><name sortKey="Karande, A A" sort="Karande, A A" uniqKey="Karande A" first="A A" last="Karande">A A Karande</name><name sortKey="Prince, P R" sort="Prince, P R" uniqKey="Prince P" first="P R" last="Prince">P R Prince</name><name sortKey="Rao, D N" sort="Rao, D N" uniqKey="Rao D" first="D N" last="Rao">D N Rao</name><name sortKey="Reddy, M V R" sort="Reddy, M V R" uniqKey="Reddy M" first="M V R" last="Reddy">M V R. Reddy</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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