The extracellular matrix protein mindin as a novel adjuvant elicits stronger immune responses for rBAG1, rSRS4 and rSRS9 antigens of Toxoplasma gondiiin BALB/c mice

Abstract

BackgroundVaccines are the most effective agents to control infections. However, recombinant vaccines often do not elicit strong immune responses. Protein antigens combined with proper adjuvants have been widely used to induce immune responses, especially the humoral immune responses, against various pathogens, including parasites. The extracellular matrix protein mindin has been recognised as an immune facilitator for initiating innate immune responses. It has therefore been expected to be a potentially potent adjuvant in the development of novel vaccines. The aim of this study was to investigate whether mindin could facilitate the induction of antigen-specific immune responses to recombinant antigens (rBAG1, rSRS4 and rSRS9) of Toxoplasma gondii in BALB/c mice.MethodsIn this study, we explored the adjuvant effect of the recombinant mindin in the generation of specific Th1 and Th2 responses to each of three T. gondii antigens, BAG1, SRS4 and SRS9. All mice in the experimental groups received either antigen alone or in combination with Freund’s adjuvant or with the recombinant mindin. The immune responses after immunisation were measured by ELISA and lymphoproliferative assays. The immunised mice were challenged with live T. gondii tachyzoites, and the protection efficiency was compared between the groups.ResultsOur results revealed that mindin as an adjuvant could facilitate the recombinant proteins to efficiently stimulate humoral and cellular responses, including antigen-specific IgG1 and IgG2a, as well as lymphocyte proliferation. Furthermore, significantly improved protection against T. gondii infection was observed in the mindin group compared with that of Freund’s adjuvant and no-adjuvant groups.ConclusionsThe extracellular matrix protein mindin can effectively induce antigen-specific humoral and cell-mediated immune responses. Our study provides a valuable basis for the development of an efficient, safe, non-toxic vaccine adjuvant for future use in humans and animals.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-429) contains supplementary material, which is available to authorized users.

Evaluation of immune protection againstToxoplasma gondiiinfection in mice induced by a multi-antigenic DNA vaccine containing TgGRA24, TgGRA25 and TgMIC6

“…In the present study, two antigen-based DNA vaccines achieved a longer survival time and greater reduction in the parasite cyst burden than a single-gene plasmid. Furthermore, a cocktail of three antigens induced a prolonged survival time and reduction in the parasite cyst burden, which was greater than that of other vaccinations using multiple antigenic peptides [29,38].…”

A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens

“…). In addition to the studies discussed here, ECM immunological research, which is expanding into the areas of prion disease, virus transmission, exosomes in viral pathogenesis and vaccine development, shows the breadth and complexity of ECM activity and regulation in infection.…”

Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice

“…However, T. gondii is an intracellular parasite, thus an immune response mediated by CD4 + Th1 and CD8 + cytotoxic T cells are the main components required to combat this parasitic infection ( Denkers and Gazzinelli, 1998 ). Immunization using animal model with recombinant expressed protein alone is weakly immunogenic ( Sloat et al, 2010 ) and often elicited a mixed Th1/Th2-like response with higher tendency of IgG1 isotype production, driving predominantly Th2-like response ( Echeverria et al, 2006 ; Dziadek et al, 2009 , 2012 ; Sun et al, 2014 ). Therefore, addition of Th1-directing adjuvant such as Complete Freund’s adjuvant (CFA) was used in this study.…”