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)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Adjuvants, Immunologic
- Antibodies, Protozoan
- Immunoglobulin G
- Lipid A
- Malaria Vaccines
- Tlr4 protein, mouse
- Toll-Like Receptor 4
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Topics |
- Adjuvants, Immunologic
(administration & dosage)
- Animals
- Antibodies, Protozoan
(blood)
- Female
- Immunoglobulin G
(blood)
- Lipid A
(administration & dosage)
- Malaria Vaccines
(administration & dosage, immunology)
- Mice
- Mice, Inbred C57BL
- Th1 Cells
(immunology)
- Toll-Like Receptor 4
(agonists)
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