Date of Award

2013-01-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Rosa A. Maldonado

Abstract

Trypanosoma cruzi is an intracellular protozoan parasite and the etiological agent for Chagas disease. Chagas is endemic in Latin America affecting 18-20 million people. However, currently worldwide increasing numbers of the disease are being seen due to migration and globalization. This neglected disease causes significant morbidity, mortality, and an economic burden. There are no known vaccines and the only currently available drug is Benznidazole, but its effects are controversial. Nonetheless, a therapeutic or prophylactic vaccine is of urgent need to alleviate this disease. In this study we present an experimental approach using a synthetic peptide-based vaccine against T. cruzi. The vaccine was developed based on a mucin-associated surface protein (MASP) (conjugated with keyhole limpet hemocyanin (KLH) [MASPsyn]. The study was done using 6-8 week female C3H/HeNHsd mice. 5 groups of mice were used: a placebo group was administered phosphate buffered saline (PBS), adjuvant controls were additionally used, in which, one group was given 0.9% aluminum hydroxide (AlOH), and another KLH. The experimental groups were separated into two groups: one with the MASPsyn, and the other with the MASPsyn and 0.9% AlOH. The parasitemia and survival of the mice were followed. After challenged with 1x105 trypomastigote Y strain, mice immunized with the MASPsyn showed 80% survival followed for 1 year. qPCR showed low parasite burden in heart, liver, and spleen (500-69 times less parasites than the placebo group before being euthanized 20-30 days post infection). The humoral response was analyzed and detection of specific anti-trypomastigote lytic antibody was detected in vaccinated mice, IgG1, IgA and IgM isotypes showed to be important in eliminating the parasite. Moreover, cytokine measurements for IL-4, IL-10, IL-12, IL-17A, and IFN-γ (relevant for resistance against the parasite) also showed to be increased in vaccinated mice. The vaccine also seems to stimulate activation of both CD4+ and CD8+ T cells. Lastly, depletion of either

CD4+ or CD8+ showed that CD8+ T cells are essential for protection. This neoteric vaccine is able to control survivability by being able to prime both a humoral and cellular immunity.

Language

en

Provenance

Received from ProQuest

File Size

66 pages

File Format

application/pdf

Rights Holder

Carylinda Serna

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Included in

Parasitology Commons

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