Immunization with Brugia malayi Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against B. malayi Infection in Mastomys coucha.

Jyoti Gupta,Shailja Misra-Bhattacharya,Sweta Misra,Ashlesh K Murthy

doi:10.1371/journal.pone.0164991

Jyoti Gupta, Shailja Misra-Bhattacharya + Show 2 more

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https://doi.org/10.1371/journal.pone.0164991

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Abstract

The current control strategies employing chemotherapy with diethylcarbamazine, ivermectin and albendazole have reduced transmission in some filaria-endemic areas, there is growing interest for complementary approaches, such as vaccines especially in light of threat of parasite developing resistance to mainstay drugs. We earlier demonstrated recombinant heavy chain myosin of B. malayi (Bm-Myo) as a potent vaccine candidate whose efficacy was enhanced by heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo) vaccination in BALB/c mice. BALB/c mouse though does not support the full developmental cycle of B. malayi, however, the degree of protection may be studied in terms of transformation of challenged infective larvae (L3) to next stage (L4) with an ease of delineating the generated immunological response of host. In the current investigation, DNA vaccination with Bm-Myo was therefore undertaken in susceptible rodent host, Mastomys coucha (M. coucha) which sustains the challenged L3 and facilitates their further development to sexually mature adult parasites with patent microfilaraemia. Immunization schedule consisted of Myo-pcD and Myo-pcD+Bm-Myo followed by B. malayi L3 challenge and the degree of protection was evaluated by observing microfilaraemia as well as adult worm establishment. Myo-pcD+Bm-Myo immunized animals not only developed 78.5% reduced blood microfilarial density but also decreased adult worm establishment by 75.3%. In addition, 75.4% of the recovered live females revealed sterilization over those of respective control animals. Myo-pcD+Bm-Myo triggered higher production of specific IgG and its isotypes which induced marked cellular adhesion and cytotoxicity (ADCC) to microfilariae (mf) and L3 in vitro. Both Th1 and Th2 cytokines were significantly up-regulated displaying a mixed immune response conferring considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccination method against LF.

Highlights

Lymphatic filariasis (LF) is one of the most morbid and debilitating parasitic disease caused by Wuchereria bancrofti, Brugia malayi and B. timori
No vaccine is in existence till date, a number of B. malayi proteins have been identified as vaccine candidates by us as well as other groups [2,3,4,5,6,7,8,9]
Within the past few years, several antigens from B. malayi have been developed as recombinant proteins and evaluated for their immunoprophylactic effectiveness [3, 27, 28] with varied success

Summary

Introduction

Lymphatic filariasis (LF) is one of the most morbid and debilitating parasitic disease caused by Wuchereria bancrofti, Brugia malayi and B. timori. B. malayi possesses a complex life cycle and engenders a complicated host immune response with varied clinical manifestations [1] To control this disease, no vaccine is in existence till date, a number of B. malayi proteins have been identified as vaccine candidates by us as well as other groups [2,3,4,5,6,7,8,9]. DNA based vaccines are relatively simple, inexpensive to produce [11] and have been shown to confer effective protection against several pathogens by inducing humoral and cellular immune responses in the immunized host. Attempts were made to enhance immunity by boosting with protein antigen that resulted in the generation of potent humoral and cellular immune responses that led to higher level of protection in veterinary and human infections [17, 18]

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