TLR4 ligand formulation causes distinct effects on antigen-specific cell-mediated and humoral immune responses

被引：28

作者：

Fox, Christopher B. ^{[1
]}

Moutaftsi, Magdalini ^{[1
]}

Vergara, Julie ^{[1
]}

Desbien, Anthony L. ^{[1
]}

Nana, Ghislain I. ^{[1
]}

Vedvick, Thomas S. ^{[1
]}

Coler, Rhea N. ^{[1
]}

Reed, Steven G. ^{[1
]}

机构：

[1] Infect Dis Res Inst, Seattle, WA 98102 USA

来源：

VACCINE | 2013年 / 31卷 / 49期

关键词：

Glucopyranosyl lipid adjuvant; Vaccine adjuvant formulation; Th1-type immunity; Oil-in-water emulsion; Liposome; Aqueous nanosuspension; FALCIPARUM CIRCUMSPOROZOITE PROTEIN; MALARIA VACCINE; DOUBLE-BLIND; DELIVERY; IMMUNOGENICITY; RTS; S/AS02A; EMULSION; PATHWAY; SAFETY; ADULTS;

D O I：

10.1016/j.vaccine.2013.09.069

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The formulation of TLR ligands and other immunomodulators has a critical effect on their vaccine adjuvant activity. In this work, the synthetic TLR4 ligand GLA was formulated with three distinct vaccine delivery system platforms (aqueous suspension, liposome, or oil-in-water emulsion). The effect of the different formulations on the adaptive immune response to protein subunit vaccines was evaluated in the context of a recombinant malaria antigen, Plasmodium berghei circumsporozoite protein (PbCSP). Antibody responses in vaccinated mice were similar for the different formulations of GLA. However, cell-mediated responses differed significantly depending on the adjuvant system; in particular, the emulsion formulation of the TLR4 ligand induced significantly enhanced cellular IFN-gamma and TNF-alpha responses compared to the other formulations. The effects of differences in adjuvant formulation composition and physical characteristics on biological activity are discussed. These results illustrate the importance of formulation of immunostimulatory adjuvants (e.g. TLR ligands) on the resulting immune responses to adjuvanted vaccines and may play a critical role for combating diseases where T cell immunity is advantageous. (C) 2013 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5848 / 5855

页数：8

相关论文

共 31 条

[1] THE ROLE OF CELL-MEDIATED IMMUNE-RESPONSES IN RESISTANCE TO MALARIA, WITH SPECIAL REFERENCE TO OXIDANT STRESS [J].

ALLISON, AC ;

EUGUI, EM .

ANNUAL REVIEW OF IMMUNOLOGY, 1983, 1 :361-392

[2] Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations [J].

Anderson, Ryan C. ;

Fox, Christopher B. ;

Dutill, Timothy S. ;

Shaverdian, Narek ;

Evers, Tara L. ;

Poshusta, Garrett R. ;

Chesko, James ;

Coler, Rhea N. ;

Friede, Martin ;

Reed, Steven G. ;

Vedvick, Thomas S. .

COLLOIDS AND SURFACES B-BIOINTERFACES, 2010, 75 (01) :123-132

[3] T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children [J].

Ansong, Daniel ;

Asante, Kwaku P. ;

Vekemans, Johan ;

Owusu, Sandra K. ;

Owusu, Ruth ;

Brobby, Naana A. W. ;

Dosoo, David ;

Osei-Akoto, Alex ;

Osei-Kwakye, Kingsley ;

Asafo-Adjei, Emmanuel ;

Boahen, Kwadwo O. ;

Sylverken, Justice ;

Adjei, George ;

Sambian, David ;

Apanga, Stephen ;

Kayan, Kingsley ;

Janssens, Michel H. ;

Lievens, Marc J. J. ;

Olivier, Aurelie C. ;

Jongert, Erik ;

Dubois, Patrice ;

Savarese, Barbara M. ;

Cohen, Joe ;

Antwi, Sampson ;

Greenwood, Brian M. ;

Evans, Jennifer A. ;

Agbenyega, Tsiri ;

Moris, Philippe J. ;

Owusu-Agyei, Seth .

PLOS ONE, 2011, 6 (04)

[4] Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns [J].

Bachmann, Martin F. ;

Jennings, Gary T. .

NATURE REVIEWS IMMUNOLOGY, 2010, 10 (11) :787-796

[5] Enhanced humoral and Type 1 cellular immune responses with Fluzone® adjuvanted with a synthetic TLR4 agonist formulated in an emulsion [J].

Baldwin, Susan L. ;

Shaverdian, Narek ;

Goto, Yasuyuki ;

Duthie, Malcolm S. ;

Raman, Vanitha S. ;

Evers, Tara ;

Mompoint, Farah ;

Vedvick, Thomas S. ;

Bertholet, Sylvie ;

Coler, Rhea N. ;

Reed, Steven G. .

VACCINE, 2009, 27 (43) :5956-5963

[6] MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020) [J].

Baudner, Barbara C. ;

Ronconi, Vanessa ;

Casini, Daniele ;

Tortoli, Marco ;

Kazzaz, Jina ;

Singh, Manmohan ;

Hawkins, Lynn D. ;

Wack, Andreas ;

O'Hagan, Derek T. .

PHARMACEUTICAL RESEARCH, 2009, 26 (06) :1477-1485

[7] Self-adjuvanting bacterial vectors expressing pre-erythrocytic antigens induce sterile protection against malaria [J].

Bergmann-Leitner, Elke S. ;

Hosie, Heather ;

Trichilo, Jessica ;

DeRiso, Elizabeth ;

Ranallo, Ryan T. ;

Alefantis, Timothy ;

Savranskaya, Tatyana ;

Grewal, Paul ;

Ockenhouse, Christian E. ;

Venkatesan, Malabi M. ;

DelVecchio, Vito G. ;

Angov, Eveline .

FRONTIERS IN IMMUNOLOGY, 2013, 4

[8] Development and Characterization of Synthetic Glucopyranosyl Lipid Adjuvant System as a Vaccine Adjuvant [J].

Coler, Rhea N. ;

Bertholet, Sylvie ;

Moutaftsi, Magdalini ;

Guderian, Jeff A. ;

Windish, Hillarie Plessner ;

Baldwin, Susan L. ;

Laughlin, Elsa M. ;

Duthie, Malcolm S. ;

Fox, Christopher B. ;

Carter, Darrick ;

Friede, Martin ;

Vedvick, Thomas S. ;

Reed, Steven G. .

PLOS ONE, 2011, 6 (01)

[9] A Synthetic Adjuvant to Enhance and Expand Immune Responses to Influenza Vaccines [J].

Coler, Rhea N. ;

Baldwin, Susan L. ;

Shaverdian, Narek ;

Bertholet, Sylvie ;

Reed, Steven J. ;

Raman, Vanitha S. ;

Lu, Xiuhua ;

DeVos, Joshua ;

Hancock, Kathy ;

Katz, Jacqueline M. ;

Vedvick, Thomas S. ;

Duthie, Malcolm S. ;

Clegg, Christopher H. ;

Van Hoeven, Neal ;

Reed, Steven G. .

PLOS ONE, 2010, 5 (10)

[10] TARGETING ANTIGEN INTO THE PHAGOCYTIC PATHWAY IN-VIVO INDUCES PROTECTIVE TUMOR-IMMUNITY [J].

FALO, LD ;

KOVACSOVICSBANKOWSKI, M ;

THOMPSON, K ;

ROCK, KL .

NATURE MEDICINE, 1995, 1 (07) :649-653

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