Identification of 38kDa Brugia malayi microfilarial protease as a vaccine candidate for lymphatic filariasis.
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.
Krithika
K N
KN
Department of Biochemistry & Jamnalal Bajaj Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sewagram 442 102, India.
Dabir
Pankaj
P
Kulkarni
Sandeep
S
Anandharaman
V
V
Reddy
M V R
MV
D000818:Animals; D000909:Antibodies, Helminth / Q000737:chemistry / Q000302:isolation & purification; D000947:Antigens, Helminth / Q000737:chemistry / Q000302:isolation & purification; D017178:Brugia malayi / Q000378:metabolism*; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D016207:Cytokines / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004605:Elephantiasis, Filarial / Q000517:prevention & control* / Q000628:therapy; D006801:Humans; D007107:Immune System; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008842:Microfilariae / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010447:Peptide Hydrolases; C506194:microfilarial protease, Brugia malayi