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Browsing College of Medicine and Public Health by Author "Abraham, David"
(Public Library of Science, 2016-07) Hess, Jessica A.; Zhan, Bin; Torigian, April R; Patton, John B; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Abraham, David; Lustigman, Sara
In some regions in Africa, elimination of onchocerciasis may be possible with mass drug
administration, although there is concern based on several factors that onchocerciasis cannot
be eliminated solely through this approach. A vaccine against Onchocerca volvulus
would provide a critical tool for the ultimate elimination of this infection. Previous studies
have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated
with alum, induced protective immunity. It was hypothesized that the levels of protective
immunity induced with the two recombinant antigens formulated with alum would be
improved by formulation with other adjuvants known to enhance different types of antigenspecific
Methodology/ Principal Findings
Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59
induced significant levels of larval killing and host protection. The immune response was
biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody.
Improved larval killing and host protection was observed in mice immunized with co-administered
Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared
to single immunizations. Antigen–specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears
that neutrophils and eosinophils participate in the protective immune response induced by
Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.
The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants
alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines,
antibody and specific effector cells. The vaccines developed in this study have the
potential of reducing the morbidity associated with onchocerciasis in humans.