Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

Susan L Baldwin; Will Roeffen; Susheel K Singh; Regis W Tiendrebeogo; Michael Christiansen; Elyse Beebe; Darrick Carter; Christopher B Fox; Randall F Howard; Steven G Reed; Robert Sauerwein; Michael Theisen

doi:10.1016/j.vaccine.2016.03.016

Synthetic TLR4 agonists enhance functional antibodies and CD4⁺ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

Susan L Baldwin, Will Roeffen, Susheel K Singh, Regis W Tiendrebeogo, Michael Christiansen, Elyse Beebe, Darrick Carter, Christopher B Fox, Randall F Howard, Steven G Reed, Robert Sauerwein, Michael Theisen

22 Citations (Scopus)

Abstract

A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.

Original language	English
Journal	Vaccine
Volume	34
Issue number	19
Pages (from-to)	2207-2215
Number of pages	9
ISSN	0264-410X
DOIs	https://doi.org/10.1016/j.vaccine.2016.03.016
Publication status	Published - 27 Apr 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.vaccine.2016.03.016

Cite this

Baldwin, S. L., Roeffen, W., Singh, S. K., Tiendrebeogo, R. W., Christiansen, M., Beebe, E., Carter, D., Fox, C. B., Howard, R. F., Reed, S. G., Sauerwein, R., & Theisen, M. (2016). Synthetic TLR4 agonists enhance functional antibodies and CD4⁺ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen. Vaccine, 34(19), 2207-2215. https://doi.org/10.1016/j.vaccine.2016.03.016

Baldwin, SL, Roeffen, W, Singh, SK , Tiendrebeogo, RW, Christiansen, M, Beebe, E, Carter, D, Fox, CB, Howard, RF, Reed, SG, Sauerwein, R & Theisen, M 2016, 'Synthetic TLR4 agonists enhance functional antibodies and CD4⁺ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen', Vaccine, vol. 34, no. 19, pp. 2207-2215. https://doi.org/10.1016/j.vaccine.2016.03.016

@article{ac62eac01110497eb1d9a2ce37eb8287,

title = "Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen",

abstract = "A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.",

author = "Baldwin, {Susan L} and Will Roeffen and Singh, {Susheel K} and Tiendrebeogo, {Regis W} and Michael Christiansen and Elyse Beebe and Darrick Carter and Fox, {Christopher B} and Howard, {Randall F} and Reed, {Steven G} and Robert Sauerwein and Michael Theisen",

year = "2016",

month = apr,

day = "27",

doi = "10.1016/j.vaccine.2016.03.016",

language = "English",

volume = "34",

pages = "2207--2215",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "19",

}

TY - JOUR

T1 - Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

AU - Baldwin, Susan L

AU - Roeffen, Will

AU - Singh, Susheel K

AU - Tiendrebeogo, Regis W

AU - Christiansen, Michael

AU - Beebe, Elyse

AU - Carter, Darrick

AU - Fox, Christopher B

AU - Howard, Randall F

AU - Reed, Steven G

AU - Sauerwein, Robert

AU - Theisen, Michael

PY - 2016/4/27

Y1 - 2016/4/27

N2 - A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.

AB - A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.

U2 - 10.1016/j.vaccine.2016.03.016

DO - 10.1016/j.vaccine.2016.03.016

M3 - Journal article

C2 - 26994314

SN - 0264-410X

VL - 34

SP - 2207

EP - 2215

JO - Vaccine

JF - Vaccine

IS - 19