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Evaluation of immune responses to a Plasmodium vivax CSP-based recombinant protein vaccine candidate in combination with second-generation adjuvants in mice.
- Source :
-
Vaccine [Vaccine] 2012 May 09; Vol. 30 (22), pp. 3311-9. Date of Electronic Publication: 2012 Mar 13. - Publication Year :
- 2012
-
Abstract
- 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.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Animals
Antibodies, Protozoan blood
CD4-Positive T-Lymphocytes immunology
Emulsions administration & dosage
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Antibody Technique, Indirect
Immunoglobulin G blood
Injections, Subcutaneous
Interferon-gamma metabolism
Interleukin-2 metabolism
Malaria Vaccines administration & dosage
Mice
Mice, Inbred C57BL
Protozoan Proteins genetics
Recombinant Proteins genetics
Recombinant Proteins immunology
Tumor Necrosis Factor-alpha metabolism
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic immunology
Adjuvants, Immunologic administration & dosage
Malaria Vaccines immunology
Plasmodium vivax immunology
Protozoan Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 30
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 22425788
- Full Text :
- https://doi.org/10.1016/j.vaccine.2012.03.004