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4. Screening of Oligomeric (Meth)acrylate Vaccine Adjuvants Synthesized via Catalytic Chain Transfer Polymerization

Author

Hege, Cordula S., primary, Stimpson, Amy, additional, Sefton, Joseph, additional, Summers, James, additional, Henke, Helena, additional, Dundas, Adam A., additional, Phan, Tony, additional, Kinsey, Robert, additional, Guderian, Jeffrey A., additional, Sivananthan, Sandra J., additional, Mohamath, Raodoh, additional, Lykins, William R., additional, Ramer-Denisoff, Gabi, additional, Lin, Susan, additional, Fox, Christopher B., additional, and Irvine, Derek J., additional

Published
2023
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7. Lyophilization process engineering and thermostability of ID93 + GLA-SE, a single-vial adjuvanted subunit tuberculosis vaccine candidate for use in clinical studies

Author

Dutill, Timothy S., primary, Archer, Michelle C., additional, McCollum, Joseph, additional, Press, Chris, additional, McNeill, Lisa, additional, Hawkins, Linda, additional, Phan, Tony, additional, Laursen, Erik D., additional, Cabullos, Richard, additional, Bouchard, Lisa, additional, Castro, Regie J., additional, Lin, Mong-Wu, additional, Roco, Jeralyn, additional, Blois, Cecile, additional, Adeagbo, Babatunde A., additional, Guderian, Jeffrey A., additional, Gerhardt, Alana, additional, Beckmann, Anna Marie, additional, Trappler, Edward H., additional, Kramer, Ryan M., additional, and Fox, Christopher B., additional

Published
2022
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8. A novel asexual blood-stage malaria vaccine candidate: PfRipr5 formulated with human-use adjuvants induces potent growth inhibitory antibodies

Author

Takashima, Eizo, primary, Nagaoka, Hikaru, additional, Correia, Ricardo, additional, Alves, Paula M., additional, Roldão, António, additional, Christensen, Dennis, additional, Guderian, Jeffrey A., additional, Fukushima, Akihisa, additional, Viebig, Nicola K., additional, Depraetere, Hilde, additional, and Tsuboi, Takafumi, additional

Published
2022
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9. Intranasal delivery of a synthetic Entamoeba histolytica vaccine containing adjuvant (LecA + GLA-3 M−052 liposomes): In vitro characterization

Author

Murphy, Brynn M., primary, Chen, John Z., additional, Rolo, Michael, additional, Eldam, Mohamed, additional, Jordan, Lynn, additional, Sivananthan, Sandra J., additional, Kinsey, Robert, additional, Guderian, Jeffrey A., additional, Pedersen, Karl, additional, Abhyankar, Mayuresh, additional, Petri, William A., additional, Fox, Christopher B., additional, Finlay, Warren H., additional, Vehring, Reinhard, additional, and Martin, Andrew R., additional

Published
2022
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14. Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy

Author

Abhyankar, Mayuresh M., primary, Orr, Mark T., additional, Kinsey, Robert, additional, Sivananthan, Sandra, additional, Nafziger, Andrew J., additional, Oakland, David N., additional, Young, Mary K., additional, Farr, Laura, additional, Uddin, Md Jashim, additional, Leslie, Jhansi L., additional, Burgess, Stacey L., additional, Liang, Hong, additional, De Lima, Ines, additional, Larson, Elise, additional, Guderian, Jeffrey A., additional, Lin, Susan, additional, Kahn, Aaron, additional, Ghosh, Prakash, additional, Reed, Sierra, additional, Tomai, Mark A., additional, Pedersen, Karl, additional, Petri, William A., additional, and Fox, Christopher B., additional

Published
2021
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15. Variable expression of immunoreactive surface proteins of Propionibacterium acnes

Author

Lodes, Michael J., Secrist, Heather, Benson, Darin R., Jen, Shyian, Shanebeck, Kurt D., Guderian, Jeffrey, Maisonneuve, Jean-Francois, Bhatia, Ajay, Persing, David, Patrick, Sheila, and Skeiky, Yasir A.W.

Subjects
Acne -- Genetic aspects, Gene expression -- Research, Genetic research, Biological sciences
Abstract

Despite accumulating data implicating Propionibacterium acnes in a variety of diseases, its precise role in infection remains to be determined. P. acnes antigen-specific CD[4.sup.+] T cells are present in early inflamed acne lesions and may be involved in the inflammatory response; however, little is known about the specific antigens involved. In this study, B cell and T cell antigens from P. acnes expression libraries were cloned and evaluated and the four predominant proteins identified were investigated. Two of these antigens share some homology with an M-like protein of Streptococcus equi and have dermatan-sulphate-binding activity (PA-25957 and 5541). The remaining two antigens, PA-21693 and 4687, are similar to the product of the Corynebacterium diphtheriae htaA gene from the hmu ABC transport locus, although only one of these (PA-21693) is encoded within an hmu-like operon and conserved amongst a range of clinical isolates. All four proteins contain an LPXTG motif, although only PA-21693 contains a characteristic sortase-sorting signal. Variation in the expression of PA-4687, 25957 and 5541 is evident amongst clinical isolates and is generated both by frameshifts associated with the putative signal peptide and by variable numbers of repeat regions toward the carboxy-terminus, potentially generating heterogeneity of molecular mass and antigenic variation. In addition, in the case of PA-25957, a frameshift in a C-rich region at the extreme carboxy-terminus eliminates the LPXTG motif in some isolates. For the dermatan-sulphate-binding PA-25957, IgG1 antibody in serum from acne-positive donors was shown to be specific for the amino-terminal region of the protein, which also contains a CD[4.sup.+] T cell epitope. In contrast, serum from ache-negative donors shows an IgG2 and IgG3 antibody subclass response to the carboxy-terminal region. These data have implications for the potential role of P. acnes in inflammatory acne and other diseases. DOI: 10.1099/mic.0.29219-0

Published
2006

16. Use of recombinant antigens for sensitive serodiagnosis of american tegumentary leishmaniasis caused by different leishmania species

Author

Sato, Camila Massae, Sanchez, Maria Carmen Arroyo, Celeste, Beatriz Julieta, Duthie, Malcolm S, Guderian, Jeffrey, Reed, Steven G, Brito, Maria Edileuza Felinto de, Campos, Marliane Batista, Encarna??o, Helia Valeria de Souza, Guerra, Jorge, Mesquita, Tirza Gabrielle Ramos de, Pinheiro, Suzana Kanawati, Ramasawmy, Rajendranath, Silveira, Fernando Tobias, Souza, Marina de Assis, and Goto, Hiro

Subjects
Prote?nas Recombinantes / gen?tica, Leishmaniose Cut?nea / diagn?stico, Leishmania / imunologia, Anticorpos Antiprotozo?rios / gen?tica, Sensibilidade e Especificidade, Testes Sorol?gicos / m?todos, Ensaio de Imunoadsor??o Enzim?tica / m?todos, Prote?nas Recombinantes / imunologia, Anticorpos Antiprotozo?rios / sangue, Anticorpos Antiprotozo?rios / imunologia
Abstract

This work was supported by Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (grant 2015/22075-8 and fellowship 2016/02622-7 to C.M.S.), by CAPES (fellowship to C.M.S.), by Conselho Nacional de Pesquisa (research fellowship to H.G.), and by Laborat?rios de Investiga??o M?dica (LIM-38-HC, FMUSP). This research was also supported by funding from the Bill and Melinda Gates Foundation under grants OPP49932 and OPP1084251 and by grant R01AI025038 from NIAID, National Institutes of Health. Universidade de S?o Paulo. Instituto de Medicina Tropical de S?o Paulo. S?o Paulo, SP, Brazil. Universidade de S?o Paulo. Instituto de Medicina Tropical de S?o Paulo. S?o Paulo, SP, Brazil. Universidade de S?o Paulo. Instituto de Medicina Tropical de S?o Paulo. S?o Paulo, SP, Brazil. Infectious Disease Research Institute. Seattle, WA, USA. Infectious Disease Research Institute. Seattle, WA, USA. Infectious Disease Research Institute. Seattle, WA, USA. Oswaldo Cruz Foundation. Aggeu Magalh?es Research Center. Department of Immunology. Recife, PE, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brazil. Funda??o de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brazil / Universidade do Estado do Amazonas. Manaus, AM, Brazil. Funda??o de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brazil Funda??o de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brazil Funda??o de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brazil / Universidade Nilton Lins. Manaus, AM, Brazil; Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. N?cleo de Medicina Tropical. Bel?m, PA, Brazil. Universidade de S?o Paulo. Instituto de Medicina Tropical de S?o Paulo. S?o Paulo, SP, Brazil / Oswaldo Cruz Foundation. Aggeu Magalh?es Research Center. Department of Immunology. Recife, PE, Brazil. Universidade de S?o Paulo. Instituto de Medicina Tropical de S?o Paulo. S?o Paulo, SP, Brazil / Universidade de S?o Paulo. Faculdade de Medicina. S?o Paulo, SP, Brazil. American tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genus Leishmania. The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayedtype hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular Leishmania species causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conserved Leishmania proteins, Leishmania (Viannia) braziliensis-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species of Leishmania prevalent in Brazil [Leishmania (Leishmania) amazonensis, L. (Viannia) braziliensis, and L. (V.) guyanensis] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL.

Published
2017

18. Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species

Author

Sato, Camila Massae, primary, Sanchez, Maria Carmen Arroyo, additional, Celeste, Beatriz Julieta, additional, Duthie, Malcolm S., additional, Guderian, Jeffrey, additional, Reed, Steven G., additional, de Brito, Maria Edileuza Felinto, additional, Campos, Marliane Batista, additional, de Souza Encarnação, Helia Valeria, additional, Guerra, Jorge, additional, de Mesquita, Tirza Gabrielle Ramos, additional, Pinheiro, Suzana Kanawati, additional, Ramasawmy, Rajendranath, additional, Silveira, Fernando Tobias, additional, de Assis Souza, Marina, additional, and Goto, Hiro, additional

Published
2017
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19. A structure-function approach to optimizing TLR4 ligands for human vaccines

Author

Carter, Darrick, primary, Fox, Christopher B, additional, Day, Tracey A, additional, Guderian, Jeffrey A, additional, Liang, Hong, additional, Rolf, Tom, additional, Vergara, Julie, additional, Sagawa, Zachary K, additional, Ireton, Greg, additional, Orr, Mark T, additional, Desbien, Anthony, additional, Duthie, Malcolm S, additional, Coler, Rhea N, additional, and Reed, Steven G, additional

Published
2016
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20. Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

Author

El Bissati, Kamal, primary, Chentoufi, Aziz A., additional, Krishack, Paulette A., additional, Zhou, Ying, additional, Woods, Stuart, additional, Dubey, Jitender P., additional, Vang, Lo, additional, Lykins, Joseph, additional, Broderick, Kate E., additional, Mui, Ernest, additional, Suzuki, Yasuhiro, additional, Sa, Qila, additional, Bi, Stephanie, additional, Cardona, Nestor, additional, Verma, Shiv K., additional, Frazeck, Laura, additional, Reardon, Catherine A., additional, Sidney, John, additional, Alexander, Jeff, additional, Sette, Alessandro, additional, Vedvick, Tom, additional, Fox, Chris, additional, Guderian, Jeffrey A., additional, Reed, Steven, additional, Roberts, Craig W., additional, and McLeod, Rima, additional

Published
2016
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21. High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

Author

Oliveira, Fabrícia Alvisi de, Silva, Carla Vanessa Oliveira, Damascena, Nayra Prata, Passos, Rodrigo Oliveira, Duthie, Malcolm, Guderian, Jeffrey, Bhatia, Ajay, and Moura, Tatiana Rodrigues de

Subjects
Metaloproteinases da Matriz, Doenças infecciosas, sCD40L, Leishmaniose visceral, CD40, Ligantes solúveis
Abstract

BACKGROUND: Soluble CD40 ligand (sCD40L) and matrix metalloproteinase 9 (MMP-9) are inflammation markers and have been poorly described in infectious disease. In this prospective study, we describe the sera kinetics of these two molecules in the course of treatment follow up in human visceral leishmaniasis (VL). METHODS: Sera from VL patients were collected before and during follow up of regular Antimony treatment. sCD40L and MMP-9 were measured by Luminex assay. Paired analysis by Wilcoxon signed test was used for comparison of values of the same subjects before and after initiation of treatment. Correlations between clinical data and parasite load with the serum levels of sCD40L and MMP-9 were performed by Spearman test. Tests were considered statistically significant if the probability of a type I error was less than 5% (p-value

Published
2013

22. Serum levels of soluble CD40 ligand and MMP-9 as markers of favorable clinical outcome in human visceral leishmaniasis

Author

Passos Rodrigo, Oliveira Fabrcia, Damascena Nayra, De Jesus Amlia, Pacheco Roque, Reed Steven, Duthie Malcolm, De Moura Tatiana, Guderian Jeffrey, Dos Santos Priscila, and Silva Carla Vanessa

Subjects
Visceral leishmaniasis, business.industry, Immunology, medicine, Immunology and Allergy, Soluble cd40l, Matrix metalloproteinase, Ligand (biochemistry), medicine.disease, business
Published
2013
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24. Treatment of canine visceral leishmaniasis by the vaccine Leish-111f + MPL-SE

Author

Santos, Joelma Trigo dos, Abbehusen, Melissa Moura Costa, Martins Netto, Eduardo, Nakatani, Maria, Sampaio, Geraldo Pedral, Jesus, Robson Silva de, Goto, Yasuyuki, Guderian, Jeffrey, Howard, Randall F., and Reed, Steven G.

Subjects
medicine.medical_specialty, Meglumine antimoniate, medicine.medical_treatment, Antiprotozoal Agents, Article, law.invention, Pharmacotherapy, Dogs, Meglumine, Randomized controlled trial, law, Internal medicine, medicine, Organometallic Compounds, Dog, Animals, Leishmania infantum, Leishmaniasis Vaccines, Adjuvant, Visceral leishmaniasis, Meglumine Antimoniate, General Veterinary, General Immunology and Microbiology, biology, business.industry, Public Health, Environmental and Occupational Health, biology.organism_classification, medicine.disease, Surgery, Vaccination, Clinical trial, Infectious Diseases, Treatment Outcome, Molecular Medicine, Leishmaniasis, Visceral, Immunotherapy, business, Vaccine, Brazil, medicine.drug
Abstract

Trabalho completo: acesso restrito, p.3333–3340 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-05-09T16:20:44Z No. of bitstreams: 1 4.pdf: 444282 bytes, checksum: 323a2175051395e734ff70b3b7a8ff84 (MD5) Made available in DSpace on 2012-05-09T16:20:44Z (GMT). No. of bitstreams: 1 4.pdf: 444282 bytes, checksum: 323a2175051395e734ff70b3b7a8ff84 (MD5) Previous issue date: 2010-04-26 Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f + MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f + MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1–3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43–95%), 64% for group 2 dogs (exact 95% CI 31–89%), and 50% for group 3 dogs (exact 95% CI 19–81%). Therapeutic efficacy of the Leish-111f + MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f + MPL-SE vaccine is a promising tool to control VL in both dogs and humans. Salvador

Published
2010
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27. High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

Author

de Oliveira, Fabrícia Alvisi, primary, Vanessa Oliveira Silva, Carla, additional, Damascena, Nayra Prata, additional, Passos, Rodrigo Oliveira, additional, Duthie, Malcolm S, additional, Guderian, Jeffrey A, additional, Bhatia, Ajay, additional, de Moura, Tatiana Rodrigues, additional, Reed, Steven G, additional, de Almeida, Roque Pacheco, additional, and de Jesus, Amélia Ribeiro, additional

Published
2013
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28. MyD88 and TRIF synergistic interaction is required for TH1-cell polarization with a synthetic TLR4 agonist adjuvant

Author

Orr, Mark T., primary, Duthie, Malcolm S., additional, Windish, Hillarie Plessner, additional, Lucas, Elyse A., additional, Guderian, Jeffrey A., additional, Hudson, Thomas E., additional, Shaverdian, Narek, additional, O'Donnell, Joanne, additional, Desbien, Anthony L., additional, Reed, Steven G., additional, and Coler, Rhea N., additional

Published
2013
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30. Design, Development and Evaluation of rK28-Based Point-of-Care Tests for Improving Rapid Diagnosis of Visceral Leishmaniasis

Author

Pattabhi, Sowmya, primary, Whittle, Jacqueline, additional, Mohamath, Raodoh, additional, El-Safi, Sayda, additional, Moulton, Garner G., additional, Guderian, Jeffrey A., additional, Colombara, Danny, additional, Abdoon, Asem O., additional, Mukhtar, Maowia M., additional, Mondal, Dinesh, additional, Esfandiari, Javan, additional, Kumar, Shailendra, additional, Chun, Peter, additional, Reed, Steven G., additional, and Bhatia, Ajay, additional

Published
2010
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37. Differential Immune Responses and Protective Efficacy Induced by Components of a Tuberculosis Polyprotein Vaccine, Mtb72F, Delivered as Naked DNA or Recombinant Protein

Author

Skeiky, Yasir A. W., primary, Alderson, Mark R., additional, Ovendale, Pamela J., additional, Guderian, Jeffrey A., additional, Brandt, Lise, additional, Dillon, Davin C., additional, Campos-Neto, Antonio, additional, Lobet, Yves, additional, Dalemans, Wilfried, additional, Orme, Ian M., additional, and Reed, Steven G., additional

Published
2004
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38. Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different LeishmaniaSpecies

Author

Sato, Camila Massae, Sanchez, Maria Carmen Arroyo, Celeste, Beatriz Julieta, Duthie, Malcolm S., Guderian, Jeffrey, Reed, Steven G., de Brito, Maria Edileuza Felinto, Campos, Marliane Batista, de Souza Encarnação, Helia Valeria, Guerra, Jorge, de Mesquita, Tirza Gabrielle Ramos, Pinheiro, Suzana Kanawati, Ramasawmy, Rajendranath, Silveira, Fernando Tobias, de Assis Souza, Marina, and Goto, Hiro

Abstract

ABSTRACTAmerican tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genus Leishmania. The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular Leishmaniaspecies causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conserved Leishmaniaproteins, Leishmania(Viannia) braziliensis-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species of Leishmaniaprevalent in Brazil [Leishmania(Leishmania) amazonensis, L. (Viannia) braziliensis, and L. (V.) guyanensis] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL.

Published
2016
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40. LeIF: A Recombinant Leishmania Protein That Induces an IL-12-Mediated Th1 Cytokine Profile

Author

Skeiky, Yasir A. W., primary, Kennedy, Mary, additional, Kaufman, David, additional, Borges, Monamaris M., additional, Guderian, Jeffrey A., additional, Scholler, John K., additional, Ovendale, Pamela J., additional, Picha, Kathleen S., additional, Morrissey, Philip J., additional, Grabstein, Kenneth H., additional, Campos-Neto, Antonio, additional, and Reed, Steven G., additional

Published
1998
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43. Optimizing manufacturing and composition of a TLR4 nanosuspension: physicochemical stability and vaccine adjuvant activity.

Author

Millie Fung, HW., Mikasa, Traci JT., Vergara, Julie, Sivananthan, Sandra J., Guderian, Jeffrey A., Duthie, Malcolm S., Vedvick, Thomas S., and Fox, Christopher B.

Subjects
IMMUNOLOGICAL adjuvants, VACCINATION, PROTOZOAN diseases, MALARIA vaccines, RAPID prototyping
Abstract

Background Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Previously, we developed a nanosuspension consisting of the synthetic TLR4 ligand glucopyranosyl lipid adjuvant (GLA) and dipalmitoyl phosphatidylcholine (DPPC). This nanosuspension is a clinical vaccine adjuvant known as GLA-AF. We examined the effects of DPPC supplier, buffer composition, and manufacturing process on GLA-AF physicochemical and biological activity characteristics. Results DPPC from different suppliers had minimal influence on physicochemical and biological effects. In general, buffered compositions resulted in less particle size stability compared to unbuffered GLA-AF. Microfluidization resulted in rapid particle size reduction after only a few passes, and 20,000 or 30,000 psi processing pressures were more effective at reducing particle size and recovering the active component than 10,000 psi. Sonicated and microfluidized batches maintained good particle size and chemical stability over 6 months, without significantly altering in vitro or in vivo bioactivity of GLA-AF when combined with a recombinant malaria vaccine antigen. Conclusions Microfluidization, compared to water bath sonication, may be an effective manufacturing process to improve the scalability and reproducibility of GLA-AF as it advances further in the clinical development pathway. Various sources of DPPC are suitable to manufacture GLAAF, but buffered compositions of GLA-AF do not appear to offer stability advantages over the unbuffered composition. [ABSTRACT FROM AUTHOR]

Published
2013
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45. Cloning, Characterization, and Serodiagnostic Evaluation of Leishmania infantumTandem Repeat Proteins

Author

Goto, Yasuyuki, Coler, Rhea N., Guderian, Jeffrey, Mohamath, Raodoh, and Reed, Steven G.

Abstract

ABSTRACTVisceral leishmaniasis (VL) is a form of leishmaniasis, which is caused by infection with the protozoan parasite Leishmania, and is often fatal unless it is treated. Rapid and accurate diagnosis of VL is important for effective treatment. Here we report the cloning of previously undescribed tandem repeat (TR) proteins of Leishmania infantumand an evaluation of VL patient antibody responses to the corresponding proteins. By screening an L. infantumexpression library with sera from human VL patients or infected hamsters, we identified 43 genes encoding B-cell antigens. Surprisingly, 19 of the 43 genes (44%) were TR proteins, and that percentage was significantly higher than that for genes picked randomly from the database. We then expressed the TR regions of LinJ16.1750, LinJ22.1590, and LinJ33.2870 and the entire LinJ28.2310 protein. These recombinant proteins were all recognized by Sudanese VL patient sera in an enzyme-linked immunosorbent assay. Recombinant LinJ16.1750 (rLinJ16.1750) showed the best performance among these antigens in terms of both sensitivity and specificity. Serological evaluation revealed that 97% (34 of 35) of Sudanese VL patients had significantly elevated antibody levels to rLinJ16.1750. Furthermore, when eight of the patient sera which had low reactivities to rK39 were tested with the novel recombinant antigens, some of the sera showed stronger antibody responses to these antigens than to rK39. Our results suggest that TR regions from the novel L. infantumproteins identified in this study are immunodominant B-cell epitopes and may represent good candidates for serodiagnosis of VL.

Published
2006
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46. ML0405 and ML2331 Are Antigens of Mycobacterium lepraewith Potential for Diagnosis of Leprosy

Author

Reece, Stephen T., Ireton, Greg, Mohamath, Raodoh, Guderian, Jeffrey, Goto, Wakako, Gelber, Robert, Groathouse, Nathan, Spencer, John, Brennan, Patrick, and Reed, Steven G.

Abstract

ABSTRACTDespite the success of multidrug therapy in reducing the number of registered leprosy cases worldwide, evidence suggests that Mycobacterium lepraecontinues to be transmitted. A serological diagnostic test capable of identifying and allowing treatment of early-stage disease could reduce transmission and prevent the onset of the disability, a common complication of the disease in later stages. Serological diagnosis based on antibody recognition of phenolic glycolipid I (PGL-I) cannot reliably identify individuals with lower bacterial indices (BI). One strategy that might improve this situation is the provision of highly specific serological antigens that may be combined with PGL-I to improve the sensitivity of diagnosis. Using serological expression cloning with a serum pool of untreated lepromatous leprosy (LL) patients, we identified 14 strongly reactive M. lepraeproteins, 5 of which were previously unstudied. We present results suggesting that two of these proteins, ML0405 and ML2331, demonstrate the ability to specifically identify LL/borderline lepromatous (BL) patients on the basis of immunoglobulin G (IgG) reactivity. In a household contact study, LL index cases were identified on the basis of this reactivity, while household contacts of these patients demonstrated undetectable reactivity. At a serum dilution of 1:800, suitable to reduce background PGL-I IgM reactivity, two BL patients with a BI of <4 showed anti-human polyvalent immunoglobulin G, A, and M reactivity measured with a combination of ML0405, ML2331, and natural disaccharide O-linked human serum albumin (NDOHSA) (synthetic PGL-I) that was markedly higher than IgM reactivity to NDOHSA alone. We suggest that ML0405 and ML2331 may have utility in serological leprosy diagnosis.

Published
2006
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47. Cloning, Expression, and Immunological Evaluation of Two Putative Secreted Serine Protease Antigens ofMycobacterium tuberculosis

Author

Skeiky, Yasir A. W., Lodes, Michael J., Guderian, Jeffrey A., Mohamath, Raodoh, Bement, Teresa, Alderson, Mark R., and Reed, Steven G.

Abstract

ABSTRACTCulture filtrate proteins (CFP) of Mycobacterium tuberculosishave been shown to contain immunogenic components that elicit at least partial protective immunity againstMycobacteriuminfection. To clone genes encoding some of the immunogenic proteins, we made a high-titer rabbit anti-CFP serum and used it to screen an M. tuberculosisgenomic expression library in Escherichia coli. In this paper, we describe the molecular cloning of two new protein components of CFP and identified them as members of the serine protease gene family. Their open reading frames contain N-terminal hydrophobic secretory signals consistent with their detection in CFP. The predicted molecular masses of the mature, fully processed forms of both antigens are ∼32 kDa, in agreement with their observed sizes on immunoblots of CFP probed with polyclonal rabbit antisera made to the recombinant proteins. Thus, these proteins have been designated MTB32A and MTB32B. Interestingly, and despite 66% amino acid sequence homology between the two proteins, polyclonal rabbit antisera made to each of the recombinant proteins were found to be specific for the respective immunizing antigens. The recombinant proteins were also evaluated in in vitro assays with donor peripheral blood mononuclear cells (PBMC) from healthy purified protein derivative (PPD)-positive individuals of diverse ethnic backgrounds. MTB32A but not MTB32B stimulated PBMC from healthy PPD-positive donors but not from PPD-negative donors to proliferate and secrete gamma interferon. MTB32A is encoded by a single-copy gene which is present in both virulent and avirulent strains of the M. tuberculosiscomplex and the BCG strain of Mycobacterium bovisbut absent in the environmental mycobacterial species tested. In addition, nucleotide sequence comparison of mtb32aof the avirulent H37Ra strain and the virulent Erdman strain, as well as with the corresponding sequences (identified in the databases) of strain H37Rv and the clinical isolate CSU93, revealed 100% identity. MTB32A, therefore, represents a candidate for inclusion in subunit vaccine development. Finally, the possible role of MTB32 serine proteases as a virulence factor(s) during Mycobacteriumspp. infection is discussed.

Published
1999
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48. Intranasal delivery of a synthetic Entamoeba histolytica vaccine containing adjuvant (LecA + GLA-3 M-052 liposomes): In vitro characterization.

Author

Murphy BM, Chen JZ, Rolo M, Eldam M, Jordan L, Sivananthan SJ, Kinsey R, Guderian JA, Pedersen K, Abhyankar M, Petri WA, Fox CB, Finlay WH, Vehring R, and Martin AR

Subjects
Adjuvants, Pharmaceutic, Adjuvants, Vaccine, Administration, Intranasal, Adult, Aerosols, Humans, Liposomes, Nasal Sprays, Reproducibility of Results, Vaccines, Synthetic, Amebiasis, Entamoeba histolytica
Abstract

Amebiasis, a disease caused by the parasite Entamoeba histolytica, is estimated to cause millions of infections and at least 55,000 deaths globally each year. With no vaccine currently available, there is an urgent need for an accessible means of stimulating protective mucosal immunity. The objective of this study was to characterize the nasal spray of a novel amebiasis vaccine candidate from a syringe-based liquid atomization device, the Teleflex MAD Nasal™, in both adult and infant nasal airways. Human ergonomic testing was completed to determine realistic actuation parameters. Spray pattern, plume geometry, and droplet size distribution were measured to evaluate reproducibility of free plume characteristics. The Alberta Idealized Nasal Inlet (AINI) and three realistic infant nasal airways were used to determine the in vitro deposition profile in adult and infant airways, respectively. Collectively, in vitro results demonstrated the feasibility of delivering the vaccine candidate to target sites within the nasal airways. Penetration through the nasal airways that could lead to deposition in the lungs was below the limit of quantification for both adult and infant geometries, indicating a low likelihood of adverse events due to lung exposure. These results support continued investigation of intranasal delivery of the synthetic Entamoeba histolytica vaccine., Competing Interests: Declaration of Competing Interest AM and WF are co-inventors of the Alberta Idealized Nasal Inlet, which is licensed to Copley Scientific. WAP is a consultant for TECHLAB, Inc. and in addition receives royalties for amebiasis diagnostics that are donated in their entirety to the American Society of Tropical Medicine and Hygiene. KP is an employee of TECHLAB, Inc. and amebiasis diagnostics are an asset of TECHLAB’s. CBF, RK, JAG, and SS are employees of AAHI, which owns assets including patents and patent applications involving formulations of GLA and 3M-052 including what is represented here. MA, WAP, and CBF are inventors on patent/patent application(s) involving compositions represented here. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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