The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.
Identifieur interne : 008702 ( Main/Exploration ); précédent : 008701; suivant : 008703The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.
Auteurs : Sabarinathan Ramachandran [Inde] ; Mishra Pankaj Kumar ; Reddy Maryada Venkata Rami ; Harinath Basker Chinnaiah ; Thomas Nutman ; Perumal Kaliraj ; James MccarthySource :
- Microbiology and immunology [ 0385-5600 ] ; 2004.
Descripteurs français
- KwdFr :
- ADN des helminthes (), ADN des helminthes (génétique), Adulte, Adulte d'âge moyen, Animaux, Brugia malayi (génétique), Brugia malayi (immunologie), Données de séquences moléculaires, Femelle, Filariose lymphatique (), Filariose lymphatique (immunologie), Filariose lymphatique (parasitologie), Humains, Mâle, Protéines d'helminthes (génétique), Protéines d'helminthes (immunologie), Protéines recombinantes (immunologie), Souris, Souris de lignée BALB C, Souris de lignée CBA, Sujet âgé, Séquence d'acides aminés, Séquence nucléotidique, Vaccination, Vaccins à ADN (immunologie), Vaccins à ADN (usage thérapeutique).
- MESH :
- génétique : ADN des helminthes, Brugia malayi, Protéines d'helminthes.
- immunologie : Brugia malayi, Filariose lymphatique, Protéines d'helminthes, Protéines recombinantes, Vaccins à ADN.
- parasitologie : Filariose lymphatique.
- usage thérapeutique : Vaccins à ADN.
- ADN des helminthes, Adulte, Adulte d'âge moyen, Animaux, Données de séquences moléculaires, Femelle, Filariose lymphatique, Humains, Mâle, Souris, Souris de lignée BALB C, Souris de lignée CBA, Sujet âgé, Séquence d'acides aminés, Séquence nucléotidique, Vaccination.
English descriptors
- KwdEn :
- Adult, Aged, Amino Acid Sequence, Animals, Base Sequence, Brugia malayi (genetics), Brugia malayi (immunology), DNA, Helminth (chemistry), DNA, Helminth (genetics), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (parasitology), Elephantiasis, Filarial (prevention & control), Female, Helminth Proteins (genetics), Helminth Proteins (immunology), Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Middle Aged, Molecular Sequence Data, Recombinant Proteins (immunology), Vaccination, Vaccines, DNA (immunology), Vaccines, DNA (therapeutic use).
- MESH :
- chemical , chemistry : DNA, Helminth.
- genetics : Brugia malayi, DNA, Helminth, Helminth Proteins.
- immunology : Brugia malayi, Elephantiasis, Filarial, Helminth Proteins, Recombinant Proteins, Vaccines, DNA.
- parasitology : Elephantiasis, Filarial.
- prevention & control : Elephantiasis, Filarial.
- chemical , therapeutic use : Vaccines, DNA.
- Adult, Aged, Amino Acid Sequence, Animals, Base Sequence, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Middle Aged, Molecular Sequence Data, Vaccination.
Abstract
Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.
PubMed: 15611611
Affiliations:
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last="Ramachandran">Sabarinathan Ramachandran</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biotechnology, Anna University, Chennai, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Centre for Biotechnology, Anna University, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumar, Mishra Pankaj" sort="Kumar, Mishra Pankaj" uniqKey="Kumar M" first="Mishra Pankaj" last="Kumar">Mishra Pankaj Kumar</name></author><author><name sortKey="Rami, Reddy Maryada Venkata" sort="Rami, Reddy Maryada Venkata" uniqKey="Rami R" first="Reddy Maryada Venkata" last="Rami">Reddy Maryada Venkata Rami</name></author><author><name sortKey="Chinnaiah, Harinath Basker" sort="Chinnaiah, Harinath Basker" uniqKey="Chinnaiah H" first="Harinath Basker" last="Chinnaiah">Harinath Basker Chinnaiah</name></author><author><name sortKey="Nutman, Thomas" sort="Nutman, Thomas" uniqKey="Nutman T" first="Thomas" last="Nutman">Thomas Nutman</name></author><author><name sortKey="Kaliraj, Perumal" sort="Kaliraj, Perumal" uniqKey="Kaliraj P" first="Perumal" last="Kaliraj">Perumal Kaliraj</name></author><author><name sortKey="Mccarthy, James" sort="Mccarthy, James" uniqKey="Mccarthy J" first="James" last="Mccarthy">James Mccarthy</name></author></analytic><series><title level="j">Microbiology and immunology</title><idno type="ISSN">0385-5600</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Sequence</term><term>Animals</term><term>Base Sequence</term><term>Brugia malayi (genetics)</term><term>Brugia malayi (immunology)</term><term>DNA, Helminth (chemistry)</term><term>DNA, Helminth (genetics)</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (parasitology)</term><term>Elephantiasis, Filarial (prevention & control)</term><term>Female</term><term>Helminth Proteins (genetics)</term><term>Helminth Proteins (immunology)</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred CBA</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Recombinant Proteins (immunology)</term><term>Vaccination</term><term>Vaccines, DNA (immunology)</term><term>Vaccines, DNA (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN des helminthes ()</term><term>ADN des helminthes (génétique)</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Brugia malayi (génétique)</term><term>Brugia malayi (immunologie)</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Filariose lymphatique ()</term><term>Filariose lymphatique (immunologie)</term><term>Filariose lymphatique (parasitologie)</term><term>Humains</term><term>Mâle</term><term>Protéines d'helminthes (génétique)</term><term>Protéines d'helminthes (immunologie)</term><term>Protéines recombinantes (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée CBA</term><term>Sujet âgé</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Vaccination</term><term>Vaccins à ADN (immunologie)</term><term>Vaccins à ADN (usage thérapeutique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA, Helminth</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Brugia malayi</term><term>DNA, Helminth</term><term>Helminth Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN des helminthes</term><term>Brugia malayi</term><term>Protéines d'helminthes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Brugia malayi</term><term>Filariose lymphatique</term><term>Protéines 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Sequence</term><term>Animals</term><term>Base Sequence</term><term>Female</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred CBA</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN des helminthes</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Filariose lymphatique</term><term>Humains</term><term>Mâle</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée CBA</term><term>Sujet âgé</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.</div></front></TEI><affiliations><list><country><li>Inde</li></country></list><tree><noCountry><name sortKey="Chinnaiah, Harinath Basker" sort="Chinnaiah, Harinath Basker" uniqKey="Chinnaiah H" first="Harinath Basker" last="Chinnaiah">Harinath Basker Chinnaiah</name><name sortKey="Kaliraj, Perumal" sort="Kaliraj, Perumal" uniqKey="Kaliraj P" first="Perumal" last="Kaliraj">Perumal Kaliraj</name><name sortKey="Kumar, Mishra Pankaj" sort="Kumar, Mishra Pankaj" uniqKey="Kumar M" first="Mishra Pankaj" last="Kumar">Mishra Pankaj Kumar</name><name sortKey="Mccarthy, James" sort="Mccarthy, James" uniqKey="Mccarthy J" first="James" last="Mccarthy">James Mccarthy</name><name sortKey="Nutman, Thomas" sort="Nutman, Thomas" uniqKey="Nutman T" first="Thomas" last="Nutman">Thomas Nutman</name><name sortKey="Rami, Reddy Maryada Venkata" sort="Rami, Reddy Maryada Venkata" uniqKey="Rami R" first="Reddy Maryada Venkata" last="Rami">Reddy Maryada Venkata Rami</name></noCountry><country name="Inde"><noRegion><name sortKey="Ramachandran, Sabarinathan" sort="Ramachandran, Sabarinathan" uniqKey="Ramachandran S" first="Sabarinathan" last="Ramachandran">Sabarinathan Ramachandran</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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