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1. ELISA with recombinant antigen Lb6H validated for the diagnosis of American tegumentary leishmaniasis

Author

Valencia-Portillo, Ruth Tamara, primary, Lindoso, José Angelo, additional, Celeste, Beatriz Julieta, additional, Bittencourt, Amanda Azevedo, additional, de Brito, Maria Edileuza Felinto, additional, Duthie, Malcolm Scott, additional, Guderian, Jeffery, additional, Guerra, Jorge, additional, Oliveira, Ana Lúcia Lyrio, additional, Reed, Steven, additional, Rocha, Mussya Cisotto, additional, Santos, Nicolle Tayná, additional, Silveira, Fernando Tobias, additional, Goto, Hiro, additional, and Sanchez, Maria Carmen Arroyo, additional

Published
2024
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3. Isolation and characterisation of Leishmania donovani protein antigens from urine of visceral leishmaniasis patients

Author

Marlais, Tegwen, primary, Bhattacharyya, Tapan, additional, Pearson, Callum, additional, Gardner, Bathsheba L., additional, Marhoon, Safiyyah, additional, Airs, Stephanie, additional, Hayes, Kiera, additional, Falconar, Andrew K., additional, Singh, Om Prakash, additional, Reed, Steven G., additional, El-Safi, Sayda, additional, Sundar, Shyam, additional, and Miles, Michael A., additional

Published
2020
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5. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations

Author

Van Hoeven, Neal, primary, Joshi, Sharvari Waghmare, additional, Nana, Ghislain Ismael, additional, Bosco-Lauth, Angela, additional, Fox, Christopher, additional, Bowen, Richard A., additional, Clements, David E., additional, Martyak, Timothy, additional, Parks, D. Elliot, additional, Baldwin, Susan, additional, Reed, Steven G., additional, and Coler, Rhea N., additional

Published
2016
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7. Soluble CD40 Ligand in Sera of Subjects Exposed to Leishmania infantum Infection Reduces the Parasite Load in Macrophages

Author

Oliveira, Fabrícia Alvisi de, primary, Barreto, Aline Silva, additional, Bomfim, Lays G. S., additional, Leite, Talita Rebeca S., additional, dos Santos, Priscila Lima, additional, Almeida, Roque Pacheco de, additional, Silva, Ângela Maria da, additional, Duthie, Malcolm S., additional, Reed, Steven G., additional, de Moura, Tatiana Rodrigues, additional, and Ribeiro de Jesus, Amélia, additional

Published
2015
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8. A Synthetic Adjuvant to Enhance and Expand Immune Responses to Influenza Vaccines

Author

Coler, Rhea N., primary, Baldwin, Susan L., additional, Shaverdian, Narek, additional, Bertholet, Sylvie, additional, Reed, Steven J., additional, Raman, Vanitha S., additional, Lu, Xiuhua, additional, DeVos, Joshua, additional, Hancock, Kathy, additional, Katz, Jacqueline M., additional, Vedvick, Thomas S., additional, Duthie, Malcolm S., additional, Clegg, Christopher H., additional, Van Hoeven, Neal, additional, and Reed, Steven G., additional

Published
2010
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9. A Full-Length Plasmodium falciparum Recombinant Circumsporozoite Protein Expressed by Pseudomonas fluorescens Platform as a Malaria Vaccine Candidate

Author

Noe, Amy R., primary, Espinosa, Diego, additional, Li, Xiangming, additional, Coelho-dos-Reis, Jordana G. A., additional, Funakoshi, Ryota, additional, Giardina, Steve, additional, Jin, Hongfan, additional, Retallack, Diane M., additional, Haverstock, Ryan, additional, Allen, Jeffrey R., additional, Vedvick, Thomas S., additional, Fox, Christopher B., additional, Reed, Steven G., additional, Ayala, Ramses, additional, Roberts, Brian, additional, Winram, Scott B., additional, Sacci, John, additional, Tsuji, Moriya, additional, Zavala, Fidel, additional, and Gutierrez, Gabriel M., additional

Published
2014
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10. DNA and Protein Co-Immunization Improves the Magnitude and Longevity of Humoral Immune Responses in Macaques

Author

Jalah, Rashmi, primary, Kulkarni, Viraj, additional, Patel, Vainav, additional, Rosati, Margherita, additional, Alicea, Candido, additional, Bear, Jenifer, additional, Yu, Lei, additional, Guan, Yongjun, additional, Shen, Xiaoying, additional, Tomaras, Georgia D., additional, LaBranche, Celia, additional, Montefiori, David C., additional, Prattipati, Rajasekhar, additional, Pinter, Abraham, additional, Bess, Julian, additional, Lifson, Jeffrey D., additional, Reed, Steven G., additional, Sardesai, Niranjan Y., additional, Venzon, David J., additional, Valentin, Antonio, additional, Pavlakis, George N., additional, and Felber, Barbara K., additional

Published
2014
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15. The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction.

Author

Cauwelaert, Natasha Dubois, Desbien, Anthony L., Hudson, Thomas E., Pine, Samuel O., Reed, Steven G., Coler, Rhea N., and Orr, Mark T.

Subjects
TOLL-like receptors, IMMUNOLOGICAL adjuvants, EMULSIONS (Pharmacy), IMMUNITY, TUBERCULOSIS vaccines, TUBERCULOSIS, LEISHMANIASIS vaccines, PROTOZOAN vaccines
Abstract

The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) promotes strong TH1 and balanced IgG1/IgG2 responses to protein vaccine antigens. This enhanced immunity is sufficient to provide protection against many diseases including tuberculosis and leishmaniasis. To better characterize the adjuvant action it is important to understand how the different cytokines and transcription factors contribute to the initiation of immunity. In the present study using T-bet-/- and IL-12-/- mice and a blocking anti-IFNαR1 monoclonal antibody, we define mechanisms of adjuvant activity of GLA-SE. In accordance with previous studies of TLR4 agonist based adjuvants, we found that TH1 induction via GLA-SE was completely dependent upon T-bet, a key transcription factor for IFNγ production and TH1 differentiation. Consistent with this, deficiency of IL-12, a cytokine canonical to TH1 induction, ablated TH1 induction via GLA-SE. Finally we demonstrate that the innate immune response to GLA-SE, including rapid IFNγ production by memory CD8+ T cells and NK cells, was contingent on type I interferon, a cytokine group whose association with TH1 induction is contextual, and that they contributed to the adjuvant activity of GLA-SE. [ABSTRACT FROM AUTHOR]

Published
2016
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17. Development and Characterization of Synthetic Glucopyranosyl Lipid Adjuvant System as a Vaccine Adjuvant

Author

Coler, Rhea N., primary, Bertholet, Sylvie, additional, Moutaftsi, Magdalini, additional, Guderian, Jeff A., additional, Windish, Hillarie Plessner, additional, Baldwin, Susan L., additional, Laughlin, Elsa M., additional, Duthie, Malcolm S., additional, Fox, Christopher B., additional, Carter, Darrick, additional, Friede, Martin, additional, Vedvick, Thomas S., additional, and Reed, Steven G., additional

Published
2011
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18. Clinical Adjuvant Combinations Stimulate Potent B-Cell Responses In Vitro by Activating Dermal Dendritic Cells

Author

Matthews, Katie, Chung, Nancy P. Y., Klasse, Per Johan, Moutaftsi, Magda, Carter, Darrick, Salazar, André M., Reed, Steven G., Sanders, Rogier W., and Moore, John P.

Subjects
IMMUNOLOGICAL adjuvants, B cells, DENDRITIC cells, CD14 antigen, VACCINATION, HUMORAL immunity, IN vitro studies
Abstract

CD14+ dermal DCs (CD14+ DDCs) have a natural capacity to activate naïve B-cells. Targeting CD14+ DDCs is therefore a rational approach for vaccination strategies aimed at improving humoral responses towards poorly immunogenic antigens, for example, HIV-1 envelope glycoproteins (Env). Here, we show that two clinically relevant TLR ligand combinations, Hiltonol plus Resiquimod and Glucopyranosyl lipid A plus Resiquimod, potently activate CD14+ DDCs, as shown by enhanced expression of multiple cytokines (IL-6, IL-10, IL-12p40 and TNF-α). Furthermore, the responses of CD14+ DDCs to these TLR ligands were not compromised by the presence of HIV-1 gp120, which can drive immunosuppressive effects in vitro and in vivo. The above TLR ligand pairs were better than the individual agents at boosting the inherent capacity of CD14+ DDCs to induce naïve B-cells to proliferate and differentiate into CD27+ CD38+ B-cells that secrete high levels of immunoglobulins. CD14+ DDCs stimulated by these TLR ligand combinations also promoted the differentiation of Th1 (IFN-γ-secreting), but not Th17, CD4+ T-cells. These observations may help to identify adjuvant strategies aimed at inducing better antibody responses to vaccine antigens, including, but not limited to HIV-1 Env. [ABSTRACT FROM AUTHOR]

Published
2013
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19. The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction.

Author

Dubois Cauwelaert N, Desbien AL, Hudson TE, Pine SO, Reed SG, Coler RN, and Orr MT

Subjects
Adjuvants, Immunologic pharmacology, Animals, Immunity, Innate drug effects, Mice, Th1 Cells immunology, Tuberculosis immunology, Glucosides pharmacology, Lipid A pharmacology, Th1 Cells drug effects
Abstract

The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) promotes strong TH1 and balanced IgG1/IgG2 responses to protein vaccine antigens. This enhanced immunity is sufficient to provide protection against many diseases including tuberculosis and leishmaniasis. To better characterize the adjuvant action it is important to understand how the different cytokines and transcription factors contribute to the initiation of immunity. In the present study using T-bet-/- and IL-12-/- mice and a blocking anti-IFNαR1 monoclonal antibody, we define mechanisms of adjuvant activity of GLA-SE. In accordance with previous studies of TLR4 agonist based adjuvants, we found that TH1 induction via GLA-SE was completely dependent upon T-bet, a key transcription factor for IFNγ production and TH1 differentiation. Consistent with this, deficiency of IL-12, a cytokine canonical to TH1 induction, ablated TH1 induction via GLA-SE. Finally we demonstrate that the innate immune response to GLA-SE, including rapid IFNγ production by memory CD8+ T cells and NK cells, was contingent on type I interferon, a cytokine group whose association with TH1 induction is contextual, and that they contributed to the adjuvant activity of GLA-SE.

Published
2016
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20. Soluble CD40 Ligand in Sera of Subjects Exposed to Leishmania infantum Infection Reduces the Parasite Load in Macrophages.

Author

de Oliveira FA, Barreto AS, Bomfim LG, Leite TR, Dos Santos PL, de Almeida RP, da Silva ÂM, Duthie MS, Reed SG, de Moura TR, and Ribeiro de Jesus A

Subjects
Antibodies, Monoclonal immunology, Antigens, Protozoan immunology, Humans, Interleukins immunology, Leishmaniasis, Visceral parasitology, Lymphocyte Activation immunology, Parasite Load methods, CD40 Ligand blood, CD40 Ligand immunology, Leishmania infantum immunology, Leishmaniasis, Visceral blood, Leishmaniasis, Visceral immunology, Macrophages immunology, Macrophages parasitology
Abstract

Background: While CD40L is typically a membrane glycoprotein expressed on activated T cells and platelets that binds and activates CD40 on the surface on antigen presenting cells, a soluble derivative (sCD40L) that appears to retain its biological activity after cleavage from cell membrane also exists. We recently reported that sCD40L is associated with clinical resolution of visceral leishmaniasis and protection against the disease. In the present study we investigated if this sCD40L is functional and exerts anti-parasitic effect in L. infantum-infected macrophages., Methodology/principal Findings: Macrophages from normal human donors were infected with L. infantum promastigotes and incubated with either sera from subjects exposed to L. infantum infection, monoclonal antibodies against human CD40L, or an isotype control antibody. We then evaluated infection by counting the number of infected cells and the number of parasites in each cell. We also measured a variety of immune modulatory cytokines in these macrophage culture supernatants by Luminex assay. The addition of sCD40L, either recombinant or from infected individuals' serum, decreased both the number of infected macrophages and number of intracellular parasites. Moreover, this treatment increased the production of IL-12, IL-23, IL-27, IL-15, and IL1β such that negative correlations between the levels of these cytokines with both the infection ratio and number of intracellular parasites were observed., Conclusions/significance: sCD40L from sera of subjects exposed to L. infantum is functional and improves both the control of parasite and production of inflamatory cytokines of infected macrophages. Although the mechanisms involved in parasite killing are still unclear and require further exploration, these findings indicate a protective role of sCD40L in visceral leishmaniasis.

Published
2015
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