A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2–A GLURP–MSP3 fusion protein malaria …

S Lousada-Dietrich, PS Jogdand, S Jepsen, VV Pinto… - Vaccine, 2011 - Elsevier
S Lousada-Dietrich, PS Jogdand, S Jepsen, VV Pinto, SB Ditlev, M Christiansen, SO Larsen…
Vaccine, 2011Elsevier
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) …
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.
Elsevier