Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis.
Identifieur interne : 000996 ( PubMed/Corpus ); précédent : 000995; suivant : 000997Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis.
Auteurs : J. Madhumathi ; P R Prince ; D N Rao ; A A Karande ; M V R. Reddy ; P. KalirajSource :
- Journal of helminthology [ 1475-2697 ] ; 2017.
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
Links to Exploration step
pubmed:26892175Le document en format XML
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Madhumathi</name><affiliation><nlm:affiliation>Department of Biotechnology,Indian Institute of Technology,Chennai-600036,India.</nlm:affiliation></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><nlm:affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry,All India Institute of Medical Sciences,New Delhi110029,India.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry,Mahatma Gandhi Institute of Medical Sciences,Sevagram442102,India.</nlm:affiliation></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. Reddy</name><affiliation><nlm:affiliation>Department of Biochemistry,Indian Institute of Science,Bangalore560012,India.</nlm:affiliation></affiliation></author><author><name sortKey="Kaliraj, P" sort="Kaliraj, P" uniqKey="Kaliraj P" first="P" last="Kaliraj">P. 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Madhumathi</name><affiliation><nlm:affiliation>Department of Biotechnology,Indian Institute of Technology,Chennai-600036,India.</nlm:affiliation></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><nlm:affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry,All India Institute of Medical Sciences,New Delhi110029,India.</nlm:affiliation></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><nlm:affiliation>Department of Biochemistry,Mahatma Gandhi Institute of Medical Sciences,Sevagram442102,India.</nlm:affiliation></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. Reddy</name><affiliation><nlm:affiliation>Department of Biochemistry,Indian Institute of Science,Bangalore560012,India.</nlm:affiliation></affiliation></author><author><name sortKey="Kaliraj, P" sort="Kaliraj, P" uniqKey="Kaliraj P" first="P" last="Kaliraj">P. Kaliraj</name><affiliation><nlm:affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of helminthology</title><idno type="eISSN">1475-2697</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Helminth (blood)</term><term>Antigens, Helminth (genetics)</term><term>Antigens, Helminth (immunology)</term><term>Disease Models, Animal</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (prevention & control)</term><term>Epitope Mapping</term><term>Epitopes, B-Lymphocyte (genetics)</term><term>Epitopes, B-Lymphocyte (immunology)</term><term>Immunoglobulin G (blood)</term><term>Murinae</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (immunology)</term><term>Treatment Outcome</term><term>Vaccines, Synthetic (administration & dosage)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Helminth</term><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Helminth</term><term>Epitopes, B-Lymphocyte</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Helminth</term><term>Epitopes, B-Lymphocyte</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Epitope Mapping</term><term>Murinae</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26892175</PMID><DateCreated><Year>2016</Year><Month>02</Month><Day>19</Day></DateCreated><DateCompleted><Year>2017</Year><Month>02</Month><Day>27</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1475-2697</ISSN><JournalIssue CitedMedium="Internet"><Volume>91</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Journal of helminthology</Title><ISOAbbreviation>J. Helminthol.</ISOAbbreviation></Journal><ArticleTitle>Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis.</ArticleTitle><Pagination><MedlinePgn>43-54</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1017/S0022149X16000055</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Madhumathi</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biotechnology,Indian Institute of Technology,Chennai-600036,India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prince</LastName><ForeName>P R</ForeName><Initials>PR</Initials><AffiliationInfo><Affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rao</LastName><ForeName>D N</ForeName><Initials>DN</Initials><AffiliationInfo><Affiliation>Department of Biochemistry,All India Institute of Medical Sciences,New Delhi110029,India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Karande</LastName><ForeName>A A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Department of Biochemistry,Mahatma Gandhi Institute of Medical Sciences,Sevagram442102,India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reddy</LastName><ForeName>M V R</ForeName><Initials>MV</Initials><AffiliationInfo><Affiliation>Department of Biochemistry,Indian Institute of Science,Bangalore560012,India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaliraj</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre for Biotechnology, Anna University,Chennai600025,India.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>02</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Helminthol</MedlineTA><NlmUniqueID>2985115R</NlmUniqueID><ISSNLinking>0022-149X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C521555">ALT-2 protein, Brugia malayi</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000909">Antibodies, Helminth</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000947">Antigens, Helminth</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018985">Epitopes, B-Lymphocyte</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007074">Immunoglobulin G</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011994">Recombinant 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