Determination of optimal prime-boost vaccination regimens against zaire ebolavirus
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Date
2013-08-29
Authors
Aviles, Jenna
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Abstract
Zaire ebolavirus is a long filamentous single-stranded RNA virus belonging to the family
Filoviridae. Due to the virus’ high mortality rate, lack of an approved vaccine, and
potential use as a bioterrorism weapon, research on this topic has been of high demand.
To address this issue, several vector platforms have been investigated as vaccine
candidates. DNA and adenovirus vaccine platforms are known to elicit robust cellmediated
immune responses, while adeno-associated virus and vesicular stomatitis virus
vaccines are recognized for strong humoral responses. The leading hypothesis of the
present project was to determine whether these four vaccination platforms, in a
heterologous prime-boost regimen, increase survival and the breadth of the immune
response. To test this hypothesis, the main objectives were to evaluate the cell-mediated
and humoral immune responses, as well as correlate the induced immunity to protection
against MA-EBOV. The heterologous pairings were strategically designed to induce
both arms of the immune response. An optimized Zaire ebolavirus glycoprotein was
inserted into each of the vaccine platforms and evaluated against mouse-adapted Zaire
ebolavirus. Serum obtained from vaccinated mice was analyzed by a neutralizing
antibody assay and IgG ELISA to determine the humoral response. The cell-mediated
immune response was monitored via ELISPOT. Collectively, the data indicates that
regardless of whether homologous or heterologous, a more robust immune response was
observed in prime-boost strategies compared to an individual vaccination alone. In
addition, the cell-mediated and humoral data show that heterologous combinations induce
higher IgG specific titers in comparison to homologous regimens. As expected and
consequent with immune responses, survival studies demonstrate that prime-boost
III
vaccinations, heterologous or homologous, are superior to vaccination regimens
involving only one strategy. This data supports further evaluation of the prime-boost
strategies to develop an optimal immunization strategy that can be applied to other
disease models.
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Keywords
Vaccine, Ebola