A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2--a GLURP-MSP3 fusion protein malaria vaccine candidate.

GMZ2 adjuvanted by aluminum hydroxide is a candidate malaria vaccine that has successfully passed phase 1 clinical testing in adult German and Gabonese volunteers and Gabonese children under five. Here we report a preclinical study screening a series of adjuvant vehicles and Toll-like receptor (TLR) agonists in CB6F1 mice to identify an improved formulation of GMZ2 suitable for further human clinical studies. GMZ2 formulated in an oil-in-water emulsion plus the synthetic TLR4 agonist GLA elicits the highest (a) vaccine-specific IgG2a and total IgG titers, (b) parasite-specific IFA titers, (c) levels of Type 1 cytokine responses (IFN-γ), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, GLA helps to elicit a vaccine-specific Type 1 antibody profile together with high levels of LLPC, both of which are thought to be essential for the development of long-term protective immunity against clinical malaria.

Lousada-Dietrich S ，Jogdand PS ，Jepsen S ，Pinto VV ，Ditlev SB ，Christiansen M ，Larsen SO ，Fox CB ，Raman VS ，Howard RF ，Vedvick TS ，Ireton G ，Carter D ，Reed SG ，Theisen M ... -  《-》

The malaria vaccine candidate GMZ2 elicits functional antibodies in individuals from malaria endemic and non-endemic areas.

Jepsen MP ，Jogdand PS ，Singh SK ，Esen M ，Christiansen M ，Issifou S ，Hounkpatin AB ，Ateba-Ngoa U ，Kremsner PG ，Dziegiel MH ，Olesen-Larsen S ，Jepsen S ，Mordmüller B ，Theisen M ... -  《-》

Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion.

Baldwin SL ，Shaverdian N ，Goto Y ，Duthie MS ，Raman VS ，Evers T ，Mompoint F ，Vedvick TS ，Bertholet S ，Coler RN ，Reed SG ... -  《-》

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 ... -  《-》

Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations.

Tamborrini M ，Stoffel SA ，Westerfeld N ，Amacker M ，Theisen M ，Zurbriggen R ，Pluschke G ... -  《MALARIA JOURNAL》