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

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-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.

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-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.

U2 - 10.1016/j.vaccine.2011.02.022

DO - 10.1016/j.vaccine.2011.02.022

M3 - Journal article

C2 - 21349366

SN - 1355-2732

SN - 1873-2518

VL - 29

SP - 3284

EP - 3292

JO - Vaccine

JF - Vaccine

IS - 17

ER -