TY - JOUR
T1 - 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
AU - Lousada-Dietrich, Susana
AU - Jogdand, Prajakta S
AU - Jepsen, Søren
AU - Valadão Vaz dos Santos Pinto, Vera Manuel
AU - Ditlev, Sisse B
AU - Christiansen, Michael
AU - Larsen, Severin Olesen
AU - Fox, Christopher B
AU - Raman, Vanitha S
AU - Howard, Randall F
AU - Vedvick, Thomas S
AU - Ireton, Gregory
AU - Carter, Darrick
AU - Reed, Steven G
AU - Theisen, Michael
N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.
PY - 2011/4/12
Y1 - 2011/4/12
N2 - 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-¿), 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.
AB - 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-¿), 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.
U2 - 10.1016/j.vaccine.2011.02.022
DO - 10.1016/j.vaccine.2011.02.022
M3 - Journal article
C2 - 21349366
VL - 29
SP - 3284
EP - 3292
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 17
ER -