Joanne M. LumsdenSaule NurmukhambetovaJennifer H. KleinJetsumon SattabongkotJason W. BennettSylvie BertholetChristopher B. FoxSteven G. ReedChristian F. OckenhouseRandall F. HowardMark E. PolhemusAnjali YadavaWalter Reed Army Institute of ResearchArmed Forces Medical Research Institute of ScienceInfectious Disease Research InstituteMahidol University2018-06-112018-06-112012-05-09Vaccine. Vol.30, No.22 (2012), 3311-3319187325180264410X2-s2.0-84859818500https://repository.li.mahidol.ac.th/handle/20.500.14594/13732Plasmodium 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. © 2012.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineVeterinaryArticleSCOPUS10.1016/j.vaccine.2012.03.004