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

Susana Lousada-Dietrich; Prajakta S Jogdand; Søren Jepsen; Vera Manuel Valadão Vaz dos Santos 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

doi:10.1016/j.vaccine.2011.02.022

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

Susana Lousada-Dietrich, Prajakta S Jogdand, Søren Jepsen, Vera Manuel Valadão Vaz dos Santos 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

44 Citations (Scopus)

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.

Original language	English
Journal	Vaccine
Volume	29
Issue number	17
Pages (from-to)	3284-92
Number of pages	9
DOIs	https://doi.org/10.1016/j.vaccine.2011.02.022
Publication status	Published - 12 Apr 2011

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Lousada-Dietrich, S., Jogdand, P. S., Jepsen, S., Valadão Vaz dos Santos Pinto, V. M., Ditlev, S. B., Christiansen, M., Larsen, S. O., Fox, C. B., Raman, V. S., Howard, R. F., Vedvick, T. S., Ireton, G., Carter, D., Reed, S. G., & Theisen, M. (2011). 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. Vaccine, 29(17), 3284-92. https://doi.org/10.1016/j.vaccine.2011.02.022

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. / Lousada-Dietrich, Susana; Jogdand, Prajakta S; Jepsen, Søren et al.

In: Vaccine, Vol. 29, No. 17, 12.04.2011, p. 3284-92.

Research output: Contribution to journal › Journal article › Research › peer-review

Lousada-Dietrich, S, Jogdand, PS, Jepsen, S, Valadão Vaz dos Santos Pinto, VM, Ditlev, SB, Christiansen, M, Larsen, SO, Fox, CB, Raman, VS, Howard, RF, Vedvick, TS, Ireton, G, Carter, D, Reed, SG & Theisen, M 2011, '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', Vaccine, vol. 29, no. 17, pp. 3284-92. https://doi.org/10.1016/j.vaccine.2011.02.022

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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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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

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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

Abstract

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