Limits...
Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

Kushwaha S, Singh PK, Rana AK, Misra-Bhattacharya S - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.

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).

Show MeSH

Related in: MedlinePlus

Reduction in Bm-TPP phosphatase activity.Recombinant Bm-TPP was pre-incubated with 10 and 20 µl (represented as open bar and closed bar respectively) of anti Bm-TPP sera and with pre-immune sera. Significant reduction in activity was noticed with anti Bm-TPP sera. Bar represents the mean ± S.E. of three replicate experiments. Statistical significance based on the differences between the mean values of immunized and control sera are indicated as *p<0.05; **p<0.01 and ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3755969&req=5

pone-0072585-g001: Reduction in Bm-TPP phosphatase activity.Recombinant Bm-TPP was pre-incubated with 10 and 20 µl (represented as open bar and closed bar respectively) of anti Bm-TPP sera and with pre-immune sera. Significant reduction in activity was noticed with anti Bm-TPP sera. Bar represents the mean ± S.E. of three replicate experiments. Statistical significance based on the differences between the mean values of immunized and control sera are indicated as *p<0.05; **p<0.01 and ***p<0.001.

Mentions: Anti-Bm-TPP serum significantly inhibited the enzyme activity by 51% and 70% respectively at 10 and 20 µl per reaction (p<0.01–0.001). Depletion of Bm-TPP specific antibody significantly (∼17–32%) reduced the inhibitory activity of anti-Bm-TPP sera. Incubation with pre- immunized or control sera did not show any significant (p>0.05) inhibition (8%) in the enzyme activity (Fig. 1).


Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

Kushwaha S, Singh PK, Rana AK, Misra-Bhattacharya S - PLoS ONE (2013)

Reduction in Bm-TPP phosphatase activity.Recombinant Bm-TPP was pre-incubated with 10 and 20 µl (represented as open bar and closed bar respectively) of anti Bm-TPP sera and with pre-immune sera. Significant reduction in activity was noticed with anti Bm-TPP sera. Bar represents the mean ± S.E. of three replicate experiments. Statistical significance based on the differences between the mean values of immunized and control sera are indicated as *p<0.05; **p<0.01 and ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3755969&req=5

pone-0072585-g001: Reduction in Bm-TPP phosphatase activity.Recombinant Bm-TPP was pre-incubated with 10 and 20 µl (represented as open bar and closed bar respectively) of anti Bm-TPP sera and with pre-immune sera. Significant reduction in activity was noticed with anti Bm-TPP sera. Bar represents the mean ± S.E. of three replicate experiments. Statistical significance based on the differences between the mean values of immunized and control sera are indicated as *p<0.05; **p<0.01 and ***p<0.001.
Mentions: Anti-Bm-TPP serum significantly inhibited the enzyme activity by 51% and 70% respectively at 10 and 20 µl per reaction (p<0.01–0.001). Depletion of Bm-TPP specific antibody significantly (∼17–32%) reduced the inhibitory activity of anti-Bm-TPP sera. Incubation with pre- immunized or control sera did not show any significant (p>0.05) inhibition (8%) in the enzyme activity (Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.

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).

Show MeSH
Related in: MedlinePlus