Effect of short-And long-Term immunization of recombinant disorganized muscle protein-1 (rDIM-1) against human filarial parasite Brugia malayi in rodents

ABSTRACT

Objective: To evaluate the effect of short-Term and long-Term immunization of recombinant disorganized muscle protein-1 (rDIM-1) in rodents against human filarial parasite Brugia malayi. Methods: Recombinant Brugia malayi DIM-1 (rDIM-1bm) protein was cloned, expressed and purified using a Ni-NTA affinity column. Mastomys coucha were immunized with rDIM-1bm in three immunization schedules short-Term (3-dose of rDIM-1bm), and long-Term (booster doses till 3-And 6-week) and subsequently challenged with infective third-stage larvae of filarial parasite Brugia malayi (L3). Microfilaraemia was monitored in L3 exposed groups on day 90 post larval inoculation (p.l.i.) and continued till day 205 p.l.i. On day 205 p.l.i. all the infected animals were killed and total worm burden was estimated. Cellular proliferative response, macrophage activity, nitric oxide (NO) release, specific IgG and its subtypes, IgE, IgA and Th1 (IFN-γ, TNF-α and IL-2) and Th2 (IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release were determined. Results: Of the 3 different immunization schedules, short-Term immunization (3-dose schedule) showed better reduction in microfilarial burden (36%-63%) in the peripheral circulation, adult worm load (52%), whereas long-Term immunization (3-And 6-week schedule) exerted less effect on peripheral microfilariae count (9%-58%), and adult worm burden (9%-12.5%). Short-Term immunization resulted in upregulation of cellular proliferation, macrophages activity, NO release, specific IgG, IgG1, IgG2a, IgG2b, IgE and IgA levels and both Th1 (IFN-γ, TNF-α and IL-2) and Th2 (IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release whereas long-Term immunization (3-And 6-week schedule) exerted less effect on parasite burden and showed mixed immunological responses. None of the rDIM-1bm administration schedules induced any pathology in lymphoid tissues, or alteration in mast cell number and granularity. Conclusions: The short-Term immunization with rDIM-1bm (3-dose schedule) induces robust immune responses and protects the host from filarial parasite infection.