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

作者：Lousada Dietrich Susana; Jogdand Prajakta S; Jepsen Soren; Pinto Vera V; Ditlev Sisse B; Christiansen Michael; Larsen Severin Olesen; Fox Christopher B; Raman Vanitha S; Howard Randall F; Vedvick Thomas S; Ireton Gregory; Carter Darrick; Reed Steven G; Theisen Michael^*

来源：Vaccine, 2011, 29(17): 3284-3292.

DOI：10.1016/j.vaccine.2011.02.022

• Malaria vaccine candidate
• Toll-like receptor agonist
• Long-lived plasma cell

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 CIA elicits the highest (a) vaccine-specific IgG2a and total IgG titers, (b) parasite-specific IFA titers, (c) levels of Type I cytokine responses (IFN-gamma), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, CIA 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.

• 出版日期2011-4-12