Abstract
Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF).
Highlights
Lymphatic filariasis (LF), a mosquito-borne parasitic disease caused by the three species of tissue dwelling filariids, Wuchereria bancrofti, Brugia malayi and B. timori is endemic in 72 countries, in the tropics and sub-tropics [1]
Serum of Bm-trehalose-6-phosphate phosphatase (TPP) immunized animals promoted significant adherence of PECs to the surface of L3 and Mf causing 7063.7% and 6561.2% cytotoxicity and death respectively within 48 h as opposed to those incubated with serum from non immunized animals (863.2% and 15.263.3% respectively) (Fig. 2A–D)
Removal of anti-Bm-TPP antibodies from the immune serum reduced (p.0.05) this cytotoxic effect to 22%63.1 and 21%62.3 respectively (Table S1)
Summary
Lymphatic filariasis (LF), a mosquito-borne parasitic disease caused by the three species of tissue dwelling filariids, Wuchereria bancrofti, Brugia malayi and B. timori is endemic in 72 countries, in the tropics and sub-tropics [1]. A likelihood approach to lessen transmission and complement MDA (Mass Drug Administration) programs could be the discovery of an effective vaccine [14,15]. The feasible concept of developing an antifilarial vaccine originates from the endemic normal individuals who despite of being continuously exposed to infective mosquito bites remain infection-free [16]. Successful immune protection has been attained in animal models after vaccination with irradiated infective larvae (L3) [17,18]. A number of B. malayi proteins have been identified as vaccine candidates and some of these offered significant degree of protection against infection in animal models [21,22,23,24,25,26,27,28,29]
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