Evaluation of immune responses to a Plasmodium vivax CSP-based recombinant protein vaccine candidate in combination with second-generation adjuvants in mice.

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.

Lumsden JM ，Nurmukhambetova S ，Klein JH ，Sattabongkot J ，Bennett JW ，Bertholet S ，Fox CB ，Reed SG ，Ockenhouse CF ，Howard RF ，Polhemus ME ，Yadava A ... -  《-》

Evaluation of the safety and immunogenicity in rhesus monkeys of a recombinant malaria vaccine for Plasmodium vivax with a synthetic Toll-like receptor 4 agonist formulated in an emulsion.

Lumsden JM ，Pichyangkul S ，Srichairatanakul U ，Yongvanitchit K ，Limsalakpetch A ，Nurmukhambetova S ，Klein J ，Bertholet S ，Vedvick TS ，Reed SG ，Sattabongkot J ，Bennett JW ，Polhemus ME ，Ockenhouse CF ，Howard RF ，Yadava A ... -  《-》

Immunological evaluation of two novel engineered Plasmodium vivax circumsporozoite proteins formulated with different human-compatible vaccine adjuvants in C57BL/6 mice.

Shabani SH ，Zakeri S ，Mortazavi Y ，Mehrizi AA ... -  《-》

New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin.

Bargieri DY ，Rosa DS ，Braga CJ ，Carvalho BO ，Costa FT ，Espíndola NM ，Vaz AJ ，Soares IS ，Ferreira LC ，Rodrigues MM ... -  《VACCINE》

IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice.

Schwenk R ，DeBot M ，Porter M ，Nikki J ，Rein L ，Spaccapelo R ，Crisanti A ，Wightman PD ，Ockenhouse CF ，Dutta S ... -  《PLoS One》