Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

Abstract

BackgroundCysteine protease inhibitors of Brugia malayi have been ascribed to be involved in parasite development as well as to immunomodulate the host’s immune response. In Onchocerca volvulus, Onchocystatin has been shown to induce partial protection in the mouse diffusion chamber vaccination model. In the present study we investigated the impact of vaccination with recombinant Bm-CPI-1 and Bm-CPI-2 proteins on protection against a subcutaneous challenge of B. malayi third stage larvae in gerbils.FindingsVaccination with E. coli derived recombinant B. malayi cysteine protease inhibitors (Bm-CPI-1 or -2) did not confer protection against B. malayi L3 challenge infection in gerbils but altered the homing of a significant number of adult worms from the lymphatics to the heart and lungs.ConclusionBm-CPI vaccination-induced alteration in worm migration is consistent with our previous observations in gerbils vaccinated with B. pahangi excretory-secretory (ES) proteins, which resulted in delayed migration of the L3s and altered the final location of adult worms. Similar observations have also been made in dogs vaccinated with Ancylostoma caninum proteins; an increased number of worms were recovered in the colon and not the expected small intestine. A change in the final niche was also reported in immune versus non-immune hosts of two other gut dwelling nematodes. Vaccination induced alteration of the parasite’s final homing might be a rare or a common phenomenon, which unfortunately is rarely recorded. The reason for the alteration in the final niche selection by adult nematode worms following vaccination is unknown and necessitates further investigation.

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part I: Helminths

“…heart and lung instead of lymphatics. As never previously reported in the literature that a vaccine induced selection of parasite' habitat, the investigators recommended further studies to explain this unique rare phenomena [205] .…”

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

“…malayi have been developed as recombinant proteins and also evaluated for their immunoprophylactic effectiveness [3, 27, 28] with varied success. Our earlier studies demonstrated moderate to high protective efficacy in some of the recombinant B .…”

Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

“…Recently, we reported that vaccination of gerbils with recombinant Bm -CPI-1 or -2 did not confer protection against B. malayi infection but rather altered the site of establishment of the developed adult worms, causing an increase in their residence in heart and lungs instead of lymphatic vessels (Arumugam et al, 2014). The reason for the lack of protective efficacy of the native Bm -CPIs vaccine is unclear, but it could be related to the known immunomodulatory property of cystatins, especially Bm -CPI-2.…”

“…Fertility was determined by measuring the levels of microfilariae (MF) in gerbil blood and by performing embryograms of female worms. The total number of worms recovered was recorded, male and female worms were differentiated and tissue location was noted upon harvest from heart, lung and various lymphatic organs as previously described (Arumugam et al, 2014). Female worm length was measured under an Olympus MVX10 microscope using the Olympus DP2-BSW software.…”

“…Antigen-specific IgG responses were determined by ELISA following the method previously described (Arumugam et al, 2014). In both experiments, a strong antigen-specific IgG response with a final end point titer of up to 1:2,048,000 was seen in sera of vaccinated animals taken post-vaccination prior to L3 challenge.…”