| Evaluation of immune responses to a Plasmodium vivax CSP-based recombinant protein vaccine candidate in combination with second-generation adjuvants in mice. | |
MedLine Citation:
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PMID: 22425788 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Plasmodium vivax is the major cause of malaria outside of sub-Saharan Africa and causes morbidity and results in significant economic impact in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of VMP001, based on the circumsporozoite protein (CSP) of P. vivax. Our interest is to evaluate second-generation vaccine formulations to identify novel combinations of adjuvants capable of inducing strong, long-lasting immune responses. In this study, groups of C57BL/6J mice were immunized subcutaneously three times with VMP001 emulsified with synthetic TLR4 (GLA) or TLR7/8 (R848) agonist in stable emulsion (SE), a combination of the TLR4 and TLR7/8 agonists, or SE alone. Sera and splenocytes were tested for the presence of antigen-specific humoral and cellular responses, respectively. All groups of mice generated high titers of anti-P. vivax IgG antibodies as detected by ELISA and immunofluorescence assay. GLA-SE promoted a shift in the antibody response to a Th1 profile, as demonstrated by the change in IgG2c/IgG1 ratio. In addition, GLA-SE induced a strong cellular immune response characterized by multi-functional, antigen-specific CD4(+) T cells secreting IL-2, TNF and IFN-γ. In contrast, mice immunized with SE or R848-SE produced low numbers of antigen-specific CD4(+) T cells, and these T cells secreted IL-2 and TNF, but not IFN-γ. Finally, R848-SE did not enhance the immune response compared to GLA-SE alone. Based on these results, we conclude that the combination of VMP001 and GLA-SE is highly immunogenic in mice and may serve as a potential second-generation vaccine candidate against vivax malaria. |
Authors:
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Joanne M Lumsden; Saule Nurmukhambetova; Jennifer H Klein; Jetsumon Sattabongkot; Jason W Bennett; Steven G Reed; Christian F Ockenhouse; Randall F Howard; Mark E Polhemus; Anjali Yadava |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-13 |
Journal Detail:
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Title: Vaccine Volume: - ISSN: 1873-2518 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8406899 Medline TA: Vaccine Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ltd. |
Affiliation:
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Malaria Vaccine Branch, Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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