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Identification of 38kDa Brugia malayi microfilarial protease as a vaccine candidate for lymphatic filariasis.

Identifieur interne : 007F78 ( Main/Exploration ); précédent : 007F77; suivant : 007F79

Identification of 38kDa Brugia malayi microfilarial protease as a vaccine candidate for lymphatic filariasis.

Auteurs : K N Krithika [Inde] ; Pankaj Dabir ; Sandeep Kulkarni ; V. Anandharaman ; M V R. Reddy

Source :

RBID : pubmed:16187525

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English descriptors

Abstract

A FPLC purified 38kDa protease (Bm mf S-7) isolated from B. malayi microfilarial soluble antigen was identified. It showed pronounced reactivity with sera collected from 'putatively immune' asymptomatic and amicrofilaraemic individuals residing in an endemic area for bancroftian filariasis. Further the immune protective activity of Bm mf S-7 antigen was evaluated in susceptible hosts, jirds (Meriones unguiculatus) against B. malayi filarial infection. The antigen showed 89% cytotoxicity against mf and 87-89% against infective (L3) larvae in in vitro antibody dependent cellular cytotoxicity Assay (ADCC) and in situ micropore chamber methods. Bm mf S-7 immunized jirds after challenge infection showed 81.5% reduction in the adult worm burden. The present study has shown that, the 38kDa microfilarial proteases (Bm mf S-7) could stimulate a strong protective immune response against microfilariae and infective larvae in jird model to block the transmission of filariasis. Analysis of IgG subclasses against Bm mf S-7 revealed a significant increase in IgG2 and IgG3 antibodies in endemic normals. Lymphocyte proliferation to Bm mf S-7 was significantly high in endemic normal group as compared to that in clinical and microfilarial carriers. Significantly enhanced levels of IFN-gamma in the culture supernatant of PBMC of endemic normals followed by stimulation with Bm mf S-7 suggest that the cellular response in this group is skewed towards Th 1 type.

PubMed: 16187525


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Le document en format XML

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<name sortKey="Krithika, K N" sort="Krithika, K N" uniqKey="Krithika K" first="K N" last="Krithika">K N Krithika</name>
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<nlm:affiliation>Department of Biochemistry & Jamnalal Bajaj Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sewagram 442 102, India.</nlm:affiliation>
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<term>Antigens, Helminth (chemistry)</term>
<term>Antigens, Helminth (isolation & purification)</term>
<term>Brugia malayi (metabolism)</term>
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<term>Cytokines (metabolism)</term>
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<term>Elephantiasis, Filarial (therapy)</term>
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<term>Immune System</term>
<term>Immunoblotting</term>
<term>Immunoglobulin G (chemistry)</term>
<term>Interferon-gamma (metabolism)</term>
<term>Interleukin-10 (metabolism)</term>
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<term>Anticorps antihelminthe (isolement et purification)</term>
<term>Antigènes d'helminthe ()</term>
<term>Antigènes d'helminthe (isolement et purification)</term>
<term>Brugia malayi (métabolisme)</term>
<term>Chromatographie d'affinité</term>
<term>Chromatographie en phase liquide</term>
<term>Cytokines (métabolisme)</term>
<term>Facteurs temps</term>
<term>Filariose lymphatique ()</term>
<term>Humains</term>
<term>Immunoglobuline G ()</term>
<term>Immunotransfert</term>
<term>Interféron gamma (métabolisme)</term>
<term>Interleukine-10 (métabolisme)</term>
<term>Interleukine-4 (métabolisme)</term>
<term>Lymphocytes auxiliaires Th1 (immunologie)</term>
<term>Microfilaria (métabolisme)</term>
<term>Peptide hydrolases ()</term>
<term>Peptide hydrolases (pharmacologie)</term>
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<term>Électrophorèse sur gel de polyacrylamide</term>
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<term>Antigens, Helminth</term>
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<term>Lymphocytes auxiliaires Th1</term>
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<term>Th1 Cells</term>
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<term>Antigènes d'helminthe</term>
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<term>Peptide Hydrolases</term>
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<term>Elephantiasis, Filarial</term>
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<term>Elephantiasis, Filarial</term>
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<term>Animals</term>
<term>Chromatography, Affinity</term>
<term>Chromatography, Liquid</term>
<term>Electrophoresis, Polyacrylamide Gel</term>
<term>Humans</term>
<term>Immune System</term>
<term>Immunoblotting</term>
<term>Time Factors</term>
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<term>Animaux</term>
<term>Anticorps antihelminthe</term>
<term>Antigènes d'helminthe</term>
<term>Chromatographie d'affinité</term>
<term>Chromatographie en phase liquide</term>
<term>Facteurs temps</term>
<term>Filariose lymphatique</term>
<term>Humains</term>
<term>Immunoglobuline G</term>
<term>Immunotransfert</term>
<term>Peptide hydrolases</term>
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<div type="abstract" xml:lang="en">A FPLC purified 38kDa protease (Bm mf S-7) isolated from B. malayi microfilarial soluble antigen was identified. It showed pronounced reactivity with sera collected from 'putatively immune' asymptomatic and amicrofilaraemic individuals residing in an endemic area for bancroftian filariasis. Further the immune protective activity of Bm mf S-7 antigen was evaluated in susceptible hosts, jirds (Meriones unguiculatus) against B. malayi filarial infection. The antigen showed 89% cytotoxicity against mf and 87-89% against infective (L3) larvae in in vitro antibody dependent cellular cytotoxicity Assay (ADCC) and in situ micropore chamber methods. Bm mf S-7 immunized jirds after challenge infection showed 81.5% reduction in the adult worm burden. The present study has shown that, the 38kDa microfilarial proteases (Bm mf S-7) could stimulate a strong protective immune response against microfilariae and infective larvae in jird model to block the transmission of filariasis. Analysis of IgG subclasses against Bm mf S-7 revealed a significant increase in IgG2 and IgG3 antibodies in endemic normals. Lymphocyte proliferation to Bm mf S-7 was significantly high in endemic normal group as compared to that in clinical and microfilarial carriers. Significantly enhanced levels of IFN-gamma in the culture supernatant of PBMC of endemic normals followed by stimulation with Bm mf S-7 suggest that the cellular response in this group is skewed towards Th 1 type.</div>
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