Evaluation of the Efficacy of Fusion or Combination Leishmania Donovani Peroxidoxin 1 and Superoxide Dismutase B1 Vaccine Candidates against Leishmaniasis in BALB/c Mice: Role of Granulocyte Macrophage Colony Stimulating Factor.
| atmire.migration.oldid | 1315 | |
| dc.contributor.advisor | Gedamu, Lashitew | |
| dc.contributor.author | Bayih, Abebe Genetu | |
| dc.date.accessioned | 2013-09-09T21:47:07Z | |
| dc.date.available | 2015-09-10T07:00:18Z | |
| dc.date.issued | 2013-09-09 | |
| dc.date.submitted | 2013 | en |
| dc.description.abstract | Leishmaniasis is a vector-borne infectious disease that affects millions of people worldwide. Human leishmaniasis appears in three major clinical forms, cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). Visceral leishmaniasis is the deadliest form with a mortality rate of about 100% in untreated clinically overt cases. The fact that people who are cured from CL develop durable protective immunity to re-infection has led to the assumption that developing effective vaccine to the disease should be feasible. However, there is no universally effective vaccine yet. Previous studies in our lab have demonstrated that amastigote-specific Leishmania donovani peroxidoxin 1 (LdPxn1) and iron superoxide dismutase B1 (LdFeSODB1) induce specific immune response and partially protect BALB/c mice when administered together with adjuvants. In this study, it was hypothesized that fusing these antigens or using them in a form of cocktail vaccine would further increase the immunogenicity and protective efficacy of the antigens. In addition, two forms of immunization strategies were compared; heterologous DNA/protein prime-boost and homologous protein/protein immunizations. Murine granulocyte macrophage colony-stimulating factor (mGMCSF) adjuvant was used in tandem fusion with the DNA vaccines. Generally, the fusion/cocktail vaccine significantly increased immunogenicity of the vaccines in both immunization protocols. However, the high immunogenicity result was not directly reflected in the protection. In DNA/protein approach, the fusion vaccine was found to be more protective than LdFeSODB1 but not LdPxn1. In protein/protein immunization, the cocktail vaccine showed lower protection than each of the individual antigens. As demonstrated by multiparameter flow cytometry, the increased immunogenicity and protection in DNA/protein immunization was correlated to induction of significantly higher number of antigen-specific CD4+ helper T cells that individually express IFN-γ, TNF-α, and IL-2 cytokines. In addition, the presence of mGMCSF adjuvant in DNA antigens generally increased immunogenicity and protective efficacy of individual or fusion vaccines as compared with the corresponding antigens without mGMCSF. Taken together, these results suggest that heterologous DNA/protein immunization with the fusion vaccine in the presence of mGMCSF adjuvant is more efficacious than protein/protein immunization with the cocktail vaccine. | en_US |
| dc.description.embargoterms | 2 years | en_US |
| dc.identifier.citation | Bayih, A. G. (2013). Evaluation of the Efficacy of Fusion or Combination Leishmania Donovani Peroxidoxin 1 and Superoxide Dismutase B1 Vaccine Candidates against Leishmaniasis in BALB/c Mice: Role of Granulocyte Macrophage Colony Stimulating Factor. (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25994 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/25994 | |
| dc.identifier.uri | http://hdl.handle.net/11023/942 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Sciences | |
| dc.subject | Microbiology | |
| dc.subject.classification | Vaccine | en_US |
| dc.subject.classification | Leishmania | en_US |
| dc.subject.classification | Peroxidoxin | en_US |
| dc.title | Evaluation of the Efficacy of Fusion or Combination Leishmania Donovani Peroxidoxin 1 and Superoxide Dismutase B1 Vaccine Candidates against Leishmaniasis in BALB/c Mice: Role of Granulocyte Macrophage Colony Stimulating Factor. | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Biological Sciences | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true |