Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen. Issue 19 (27th April 2016)

• Record Type: Journal Article
• Authors: Baldwin, Susan L.; Roeffen, Will; Singh, Susheel K.; Tiendrebeogo, Regis W.; Christiansen, Michael; Beebe, Elyse; Carter, Darrick; Fox, Christopher B.; Howard, Randall F.; Reed, Steven G.; Sauerwein, Robert; Theisen, Michael
• Is Part Of: Vaccine. Volume 34:Issue 19(2016)
• Page Start: 2207
• Page End: 2215
• Publication Date: 2016-04-27
• Subjects: Plasmodium falciparum -- GMZ2 -- Pfs48/45 -- Transmission blocking -- CD4 T-helper cells -- GLA -- SLA; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.03.016
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A multistage chimera consisting of transmission and asexual blood-stage antigens. This chimera consists of P. falciparum GMZ2 genetically fused to Pf s48/45-6C fragment. GMZ2 is in advanced clinical trials. The GMZ2- Pf s48/45-6C chimera elicits functional antibodies in small rodents. Formulations containing GLA or SLA elicited the strongest immune responses. Abstract: 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 Pf s48/45-6C 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-γ responses in CD4+ TH 1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.