The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.
Identifieur interne : 004A58 ( PubMed/Corpus ); précédent : 004A57; suivant : 004A59The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.
Auteurs : W F Gregory ; A K Atmadja ; J E Allen ; R M MaizelsSource :
- Infection and immunity [ 0019-9567 ] ; 2000.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antigens, Helminth (genetics), Base Sequence, Brugia malayi (genetics), Brugia malayi (growth & development), Brugia malayi (immunology), Caenorhabditis elegans (genetics), Caenorhabditis elegans (immunology), DNA Primers (genetics), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (parasitology), Elephantiasis, Filarial (prevention & control), Gene Expression Regulation, Developmental, Genetic Variation, Gerbillinae, Helminth Proteins (genetics), Helminth Proteins (immunology), Humans, Immunization, Introns, Larva (genetics), Larva (immunology), Male, Molecular Sequence Data, Sequence Homology, Amino Acid, Vaccines (genetics).
- MESH :
- chemical , genetics : Antigens, Helminth, DNA Primers, Helminth Proteins, Vaccines.
- genetics : Brugia malayi, Caenorhabditis elegans, Larva.
- growth & development : Brugia malayi.
- immunology : Brugia malayi, Caenorhabditis elegans, Elephantiasis, Filarial, Helminth Proteins, Larva.
- parasitology : Elephantiasis, Filarial.
- prevention & control : Elephantiasis, Filarial.
- Amino Acid Sequence, Animals, Base Sequence, Gene Expression Regulation, Developmental, Genetic Variation, Gerbillinae, Humans, Immunization, Introns, Male, Molecular Sequence Data, Sequence Homology, Amino Acid.
Abstract
Lymphatic filariasis is a major tropical disease caused by the mosquito-borne nematodes Brugia and Wuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Vaccines against filariasis must generate immunity to the infective mosquito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic-dwelling adult parasites. We have identified two highly expressed genes, designated abundant larval transcript-1 and -2 (alt-1 and alt-2), from each of which mRNAs account for >1% of L3 cDNAs. ALT-1 and ALT-2 share 79% amino acid identity across 125 residues, including a putative signal sequence and a prominent acidic tract. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. Humans exposed to Brugia malayi show a high frequency of immunoglobulin G1 (IgG1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-stage antigens, which are targeted by the IgG4 isotype. Immunization of susceptible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survival, the highest reported for a single antigen from any filarial parasite. ALT-1 and the closely related ALT-2 are therefore strong candidates for a future vaccine against human filariasis.
PubMed: 10858234
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pubmed:10858234Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.</title><author><name sortKey="Gregory, W F" sort="Gregory, W F" uniqKey="Gregory W" first="W F" last="Gregory">W F Gregory</name><affiliation><nlm:affiliation>Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Atmadja, A K" sort="Atmadja, A K" uniqKey="Atmadja A" first="A K" last="Atmadja">A K Atmadja</name></author><author><name sortKey="Allen, J E" sort="Allen, J E" uniqKey="Allen J" first="J E" last="Allen">J E Allen</name></author><author><name sortKey="Maizels, R M" sort="Maizels, R M" uniqKey="Maizels R" first="R M" last="Maizels">R M Maizels</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:10858234</idno><idno type="pmid">10858234</idno><idno type="wicri:Area/PubMed/Corpus">004A58</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">004A58</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.</title><author><name sortKey="Gregory, W F" sort="Gregory, W F" uniqKey="Gregory W" first="W F" last="Gregory">W F Gregory</name><affiliation><nlm:affiliation>Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Atmadja, A K" sort="Atmadja, A K" uniqKey="Atmadja A" first="A K" last="Atmadja">A K Atmadja</name></author><author><name sortKey="Allen, J E" sort="Allen, J E" uniqKey="Allen J" first="J E" last="Allen">J E Allen</name></author><author><name sortKey="Maizels, R M" sort="Maizels, R M" uniqKey="Maizels R" first="R M" last="Maizels">R M Maizels</name></author></analytic><series><title level="j">Infection and immunity</title><idno type="ISSN">0019-9567</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antigens, Helminth (genetics)</term><term>Base Sequence</term><term>Brugia malayi (genetics)</term><term>Brugia malayi (growth & development)</term><term>Brugia malayi (immunology)</term><term>Caenorhabditis elegans (genetics)</term><term>Caenorhabditis elegans (immunology)</term><term>DNA Primers (genetics)</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (parasitology)</term><term>Elephantiasis, Filarial (prevention & control)</term><term>Gene Expression Regulation, Developmental</term><term>Genetic Variation</term><term>Gerbillinae</term><term>Helminth Proteins (genetics)</term><term>Helminth Proteins (immunology)</term><term>Humans</term><term>Immunization</term><term>Introns</term><term>Larva (genetics)</term><term>Larva (immunology)</term><term>Male</term><term>Molecular Sequence Data</term><term>Sequence Homology, Amino Acid</term><term>Vaccines (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Helminth</term><term>DNA Primers</term><term>Helminth Proteins</term><term>Vaccines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Brugia malayi</term><term>Caenorhabditis elegans</term><term>Larva</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Brugia malayi</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Brugia malayi</term><term>Caenorhabditis elegans</term><term>Elephantiasis, Filarial</term><term>Helminth Proteins</term><term>Larva</term></keywords><keywords scheme="MESH" qualifier="parasitology" 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>Amino Acid Sequence</term><term>Animals</term><term>Base Sequence</term><term>Gene Expression Regulation, Developmental</term><term>Genetic Variation</term><term>Gerbillinae</term><term>Humans</term><term>Immunization</term><term>Introns</term><term>Male</term><term>Molecular Sequence Data</term><term>Sequence Homology, Amino Acid</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphatic filariasis is a major tropical disease caused by the mosquito-borne nematodes Brugia and Wuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Vaccines against filariasis must generate immunity to the infective mosquito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic-dwelling adult parasites. We have identified two highly expressed genes, designated abundant larval transcript-1 and -2 (alt-1 and alt-2), from each of which mRNAs account for >1% of L3 cDNAs. ALT-1 and ALT-2 share 79% amino acid identity across 125 residues, including a putative signal sequence and a prominent acidic tract. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. Humans exposed to Brugia malayi show a high frequency of immunoglobulin G1 (IgG1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-stage antigens, which are targeted by the IgG4 isotype. Immunization of susceptible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survival, the highest reported for a single antigen from any filarial parasite. ALT-1 and the closely related ALT-2 are therefore strong candidates for a future vaccine against human filariasis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10858234</PMID><DateCreated><Year>2000</Year><Month>07</Month><Day>20</Day></DateCreated><DateCompleted><Year>2000</Year><Month>07</Month><Day>20</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0019-9567</ISSN><JournalIssue CitedMedium="Print"><Volume>68</Volume><Issue>7</Issue><PubDate><Year>2000</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Infection and immunity</Title><ISOAbbreviation>Infect. Immun.</ISOAbbreviation></Journal><ArticleTitle>The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.</ArticleTitle><Pagination><MedlinePgn>4174-9</MedlinePgn></Pagination><Abstract><AbstractText>Lymphatic filariasis is a major tropical disease caused by the mosquito-borne nematodes Brugia and Wuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Vaccines against filariasis must generate immunity to the infective mosquito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic-dwelling adult parasites. We have identified two highly expressed genes, designated abundant larval transcript-1 and -2 (alt-1 and alt-2), from each of which mRNAs account for >1% of L3 cDNAs. ALT-1 and ALT-2 share 79% amino acid identity across 125 residues, including a putative signal sequence and a prominent acidic tract. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. Humans exposed to Brugia malayi show a high frequency of immunoglobulin G1 (IgG1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-stage antigens, which are targeted by the IgG4 isotype. Immunization of susceptible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survival, the highest reported for a single antigen from any filarial parasite. ALT-1 and the closely related ALT-2 are therefore strong candidates for a future vaccine against human filariasis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gregory</LastName><ForeName>W F</ForeName><Initials>WF</Initials><AffiliationInfo><Affiliation>Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Atmadja</LastName><ForeName>A K</ForeName><Initials>AK</Initials></Author><Author ValidYN="Y"><LastName>Allen</LastName><ForeName>J E</ForeName><Initials>JE</Initials></Author><Author ValidYN="Y"><LastName>Maizels</LastName><ForeName>R M</ForeName><Initials>RM</Initials></Author></AuthorList><Language>eng</Language><DataBankList 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UI="D015801">Helminth Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014612">Vaccines</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Am J Trop Med Hyg. 1985 Nov;34(6):1132-7</RefSource><PMID Version="1">3834797</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Biochem Parasitol. 1996 Jan;75(2):221-9</RefSource><PMID Version="1">8992320</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Parasitol Today. 1991 Dec;7(12):341-3</RefSource><PMID Version="1">15463411</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 1989 Jan;83(1):14-22</RefSource><PMID Version="1">2642916</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Parasitol Today. 1991 Oct;7(10):271-6</RefSource><PMID 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