DNA Immunization with the Gene Encoding SM21. 7 Protein Protects Mice Against Schistosoma mansoni Infections

Journal of American Science DNA Immunization Against Achistosome Infections 01/2006; 2.


The current focus of schistosomiasis research is to develop a vaccine that will significantly reduce the incidence of disease. Immunization with DNA is a new trend in vaccine development that could enhance the safety and efficacy of currently used vaccines. The immunogenicity and protective efficacy of a DNA vaccine encoding the antigen SM21.7 was evaluated in C57 BL/6 and Swiss albino mice. The ORF of SM21.7 has been cloned into the eukaryotic expression vector pcDNA 1/Amp under control of CMV late enhancer promoter. The groups of mice were vaccinated intramuscularly with SM21.7-pcDNA1 and boosted twice shown high and specific humoral response in comparison with control (blank pcDNA1/Amp). The level of anti SM21.7 antibody in immunized mice at weeks 3, 6 and 9 intervals post-immunization was significantly higher than in control group. The maximum level of antibodies was obtained at 7 weeks post -challenge infection. Sera from immunized mice could recognize the SM21.7 protein and the specific antibodies were able to mediate a significant killing of schistosomula using peritoneal macrophages as effector cells. In contrast the preimmune sera and sera control serum had no specific reactivity to SM21.7 protein. Immunization with SM21.7-pcDNA conferred a significant level of protection against challenge (41,53%) in Swiss Albino and C57BL/6 mice respectively. Histopathological examination of the vaccinated liver revealed a decreased in the number, size and change in the cellularity of the granuloma compared to the control infected liver. In addition reductions in worm viability, worm fecundity and egg hatching ability have been observed following challenge with S. mansoni cercariae. The number of eggs in the liver and intestine was reduced by 62% and 67% respectively compared to control group. The results suggested that SM21.7 might be a candidate antigen for the generation of antipathology vaccine against schistosomes. [The Journal of American Science. 2006;2(4):59-69].

Download full-text


Available from: Mohamed Saber
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schistosomiasis control currently relies primarily on chemotherapy which is both expensive and temporary; therefore there is an urgent need for an effective vaccine. One of the main strategies for vaccine development is the identification of specific antigen(s) that elicit highly protective immune response in immunized hosts. Several defined vaccine candidate antigens of Schistosoma mansoni have shown promise in animal vaccination experiments. In a previous study, single-gene vaccination with SMS01 recombinant protein was shown to elicit partial protection against Schistosoma mansoni challenge infection. Here we show that the vaccination of mice with a SMS01 (Sm21.7) vaccine cocktail significantly enhance protective responses against S. mansoni infection. To evaluate the usefulness of combined SMS01 DNA and protein as a cocktail vaccine against infection, the vaccination models were applied using DNA vaccination and SMS01 fusion protein or both. Consequently, the gene coding for SMS01 immunogenic protein inserted into mammalian expression vector pcDNA1, used as DNA vaccine, in combination with recombinant protein produced in pET-3a system. Then the ability of these combinations to induce a protection against S. mansoni infection was analyzed according to worm reduction rate and egg reduction rate after vaccination of mice. In addition the level of IgG antibody response was determined by ELISA. Results showed a significant reduction in worm burden in animals immunized with protein, DNA or combined vaccine, has been observed as 63%, 55% and 46% respectively compared to the control group. ELISA results showed that all the vaccinated groups have produced a high IgG titre and the highest IgG titre was produced by fusion protein group when compared to the control. Antifecundity effects of the three treatments have been observed, and the oogram pattern indicated that the dead ova were very high and the highest level was obtained using fusion protein. In spite of this result, the advantages of DNA vaccination model cannot be denied as being easier and economic. Thus, vaccination against S. mansoni remains a long-term prospect because wide ranges of time and tremendous amount of work are needed for continuous development and optimization of vaccine cocktails. [The Journal Of American Science. 2007;3(4):113-126]. (ISSN: 1545-1003).
    Full-text · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Recent large-scale efforts aimed at limiting schistosomiasis have produced limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes such as Cu-Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection, as a prelude for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. PBMC, mesenteric and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. These data demonstrate the potential of antioxidants as vaccine candidates.
    Full-text · Article · Jun 2015 · Frontiers in Immunology