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.
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| Abstract |
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.
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| Authors | Susana Lousada-Dietrich, Prajakta S Jogdand, Søren Jepsen, Vera V Pinto, Sisse B Ditlev, Michael Christiansen, Severin Olesen Larsen, Christopher B Fox, Vanitha S Raman, Randall F Howard, Thomas S Vedvick, Gregory Ireton, Darrick Carter, Steven G Reed, Michael Theisen |
| Journal | Vaccine (Vaccine) Vol. 29 Issue 17 Pg. 3284-92 (Apr 12 2011) ISSN: 1873-2518 [Electronic] Netherlands |
| PMID | 21349366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
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