The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice
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Date
2016-07
Authors
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
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Rights
Copyright © 2016 Hess et al.
Rights Holder
The authors
Abstract
Background
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
immune responses.
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.
Conclusions/Significance
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.
Description
This is an open
access article distributed under the terms of the
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unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Keywords
Immunomodulatory Role of Adjuvants, Adjuvants, Vaccines, Recombinant Antigens
Citation
Hess JA, Zhan B, Torigian AR, et al. The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice. McSorley HJ, ed. PLoS Neglected Tropical Diseases. 2016;10(7):e0004797. doi:10.1371/journal.pntd.0004797.