Oral Vaccination withSalmonella entericaas a Cruzipain-DNA Delivery System Confers Protective Immunity againstTrypanosoma cruzi

Abstract

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-␥) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4 ؉ or CD8 ؉ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-␥ and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.

Prime-boost immunization with cruzipain co-administered with MALP-2 triggers a protective immune response able to decrease parasite burden and tissue injury in an experimental Trypanosoma cruzi infection model

“…Accordingly, rCz-vaccinated animals from this group presented no inflammatory infiltrates in their striated muscles. Encouraging results have also been recently reported by our group using Salmonella-mediated delivery of a Cz-based DNA vaccine [41]. However, it would be difficult to implement such approach in the field.…”

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

“…Mucosal vaccines using commensal bacteria rely on its endogenous regulation being transferred to the vaccine antigen (40). Vaccines based on attenuated bacterial pathogens, especially live Salmonellabased oral vaccines, have demonstrated the ability to induce protective mucosal and systemic immune responses (6,14,52,61,63). However, public fear of using an attenuated pathogen as a vaccine carrier has deterred its acceptance.…”

Active and Passive Immunizations withBordetellaColonization Factor A Protect Mice against Respiratory Challenge withBordetella bronchiseptica

“…In all of the vaccinated mice, IgG2a was detected, whereas IgG1 was the major isotype in the hyperimmune BcfA-specific rat serum. Although the correlation between induction of different IgG subclasses and Th1/Th2 activity has not been extensively characterized, IgG2a in the mouse and IgG1 in the rat are Th1 cytokine-driven antibody subclass (7,10,36). Very little is known about specific cellular immune responses generated as a result of vaccination with B. bronchiseptica proteins.…”