Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen
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Publication year
2016Source
Vaccine, 34, 19, (2016), pp. 2207-15ISSN
Publication type
Article / Letter to editor
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Organization
Medical Microbiology
Journal title
Vaccine
Volume
vol. 34
Issue
iss. 19
Page start
p. 2207
Page end
p. 15
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life SciencesAbstract
A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-gamma responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-gamma and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.
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- Faculty of Medical Sciences [93198]
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