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

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.

Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis

“…Additionally, since natural infection of cattle with O. ochengi results in no known negative pathological effects on the host, it is not possible from this study to determine the benefits of this co-administered vaccine from a therapeutic perspective [24]. However, irrespective of whether the observed reduction in Mf burdens is the result of inhibition of larval development, adult female and/or Mf effect(s) or some combination of these, our findings highlight the potential benefits of using these vaccines candidates in terms of an anti-fecundity effect as was observed in experimental B. malayi vaccine studies [16,51,52]. In humans, this would help to reduce disease pathology associated with microfilaridermia, and also greatly assist ongoing elimination efforts through lowering of O. volvulus transmission.…”

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

“…A prophylactic vaccine has the potential to protect the at-risk population from getting the infection and possibly boost immunity by natural exposure to a low-level infection in endemic areas. Our group and others have been working during the last decade to develop an effective prophylactic vaccine against LF (Denham, 1980; Dissanayake et al, 1995; Gregory et al, 1997; Anand et al, 2008; Gnanasekar et al, 2008; Vedi et al, 2008; Veerapathran et al, 2009; Anand et al, 2011; Kalyanasundaram and Balumuri, 2011; Babayan et al, 2012; Dakshinamoorthy et al, 2012; Anugraha et al, 2013; Dakshinamoorthy et al, 2013a; Gomase et al, 2013; Arumugam et al, 2014; Gupta et al, 2016). A multivalent r Bm HAT vaccine developed in our laboratory showed significant protection against challenge infections in rodent models (Dakshinamoorthy and Kalyanasundaram, 2013; Dakshinamoorthy et al, 2013a).…”

“…These findings brought to light the critical need for a more sustainable approach such as a prophylactic vaccine together with MDA to interrupt the transmission and control of LF infection in endemic areas (Ramaswamy 2016). Our laboratory and others have identified and characterized several potential candidate vaccine antigens of LF and evaluated their vaccine potential in rodent models (Denham, 1980; Dissanayake et al, 1995; Gregory et al, 1997; Anand et al, 2008, 2011; Gnanasekar et al, 2008; Vedi et al, 2008; Veerapathran et al, 2009; Kalyanasundaram and Balumuri, 2011; Babayan et al, 2012; Dakshinamoorthy et al, 2012; Anugraha et al, 2013; Dakshinamoorthy et al, 2013a; Gomase et al, 2013; Arumugam et al, 2014; Gupta et al, 2016). Among the various antigens that we characterized, four antigens, abundant larval transcript-2 (ALT-2) (Anand et al, 2008; Kalyanasundaram and Balumuri, 2011; Madhumathi et al, 2017), heat shock protein (HSP) 12.6 (Dakshinamoorthy et al, 2012), thioredoxin peroxidase-2 (TPX-2) (Anand et al, 2008; Anugraha et al, 2013) and tetraspanin large extracellular loop (TSP-LEL) (Gnanasekar et al, 2008; Dakshinamoorthy et al, 2013a) gave excellent protection in rodent models.…”

Promising Technologies in the Field of Helminth Vaccines

“…An initial endeavor gave two immunizations of DNA followed by two protein boosts adjuvanted by Freund’s incomplete adjuvant (FIA). This vaccine reduced parasite burden by 75.3% and showed a 78.5% reduction in microfilarial density in the blood ( 154 ). Antibody responses were shown to kill L3 larvae, and cytokines IL2, IFNγ, TNFα, IL12, IL4 and IL10 were increased after immunization and maintained through challenge.…”