Item request has been placed!
×
Item request cannot be made.
×

Mucin-associated surface protein as a vaccine against chagas disease
Item request has been placed!
×
Item request cannot be made.
×

- Publication Date:May 07, 2019
- Additional Information
- Patent Number: 10279,023
- Appl. No: 15/430716
- Application Filed: February 13, 2017
- Abstract: Use of synthetic peptides derived from Trypanosoma cruzi antigens and their use in vaccination against trypomastigote infection and Chagas disease. T. cruzi uses several surface proteins to invade the host. In their role of protection, the surface protients ensure the targeting and invasion of specific cells or tissues. A conserved region in the family of mucin-associated surface proteins (MASP) was used to analyze the expression of MASP at different points of invasion and proved to be important for host cell invasion, thus suggesting MASP as a candidate for vaccine development. A synthetic peptide, MASPsyn, was studied and showed efficacy in stimulating antibody and cytokine production necessary for resistance against the parasite.
- Inventors: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX, US)
- Assignees: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX, US)
- Claim: 1. A pharmaceutical composition comprising: a peptide consisting of the amino acid sequence selected from SEQ ID NO: 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, wherein the peptide is a variant of SEQ ID NO: 1; and an immune-effective amount of (i) an adjuvant or (ii) a conjugate of said peptide.
- Claim: 2. The pharmaceutical composition of claim 1 wherein the adjuvant is aluminum hydroxide.
- Claim: 3. The pharmaceutical composition of claim 1 wherein the peptide is conjugated to keyhole limpet hemocyanin.
- Patent References Cited: 4298596 November 1981 Snary
9566320 February 2017 Maldonado
2010/0297186 November 2010 De Baeremaecher Barros
2011/0028901 February 2011 Estes et al.
2011/0166063 July 2011 Bossard et al.
2012/0258126 October 2012 Scholler et al. - Other References: El-Sayed et al., Science, 2005; 309: 409-415. cited by examiner
Stills, ILAR Journal, 2005; 46(3): 281-293. cited by examiner
Harris et al., Micron, 1999; 30: 597-623. cited by examiner
Abbas, A. K. et al, Functional diversity of helper T lymphocytes: Nature (1996) 383:787-793. cited by applicant
Abrahamsohn, I. A. et al. “Trypanosoma cruzi: IL-10, TNF, IFN-γ. and IL-12 Regulate Innate and Acquired Immunity to Infection,” Experimental Parasitology (1996) 84:231-144. cited by applicant
Abrahamsohn, I.S. et al. “Effects of Interleukin-4 Deprivation and Treatment on Resistance to Trypanosoma cruz,” Infection and Immunity (2000) 68(4):1975-1979. cited by applicant
Acost A-Serrano. A. et al.. “Comparison and Evolution of the Surface Architecture of Trypanosomatid Parasites.” Trypanosomes—After the Genome (2007), D. Barry, J. Mottram, R McCulloch, and A. Acosta-Serrano (Eds.). Horizon Scientific Press. Norwich, UK. pp. 315-333. cited by applicant
Aliberti, J. C. S. et al., “Interleukin-12 Mediates Resistance to Trypanosoma cruzi in Mice and is Produced by Murine Macrophages in Response to Live Trypomastigotes.” Infection and Immunity (1996) 64(6): 1961-1967. cited by applicant
Almeida, I. C. et al., “Complement-Mediated Lysis of Trypanosoma cruzi Trypomastigotes by Human Anti-α-Galactosyl Antibodies,” The Journal of Immunology (1991) 146(7):2394-2400. cited by applicant
Almeida, I. C. et al., “Lytic anti-α-galactosyl antibodies from patients with chronic Chagas' disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi.” Biochem. J. (1994) 304:793-802. cited by applicant
Almeida, I. C. et al., “A highly sensitive and specific chemiluminescent enzyme-linked immunosorbent assay for diagnosis of active Trypanosoma cruzi infection,” Transfusion (1997) 37:850-857. cited by applicant
Almeida. I. C. et al.. “Glycoconjugates of Trypanosoma cruzi: A 74 kD Antigen of trypomastigotes Specifically Reacts with Lytic Anti-α-Galactosyl Antibodies from Patients with Chronic Chagas Disease,” Journal of Clinical Laboratory Analysis (1993) y:307-316. cited by applicant
Alsford, S. et al., “Genetic dissection of drug resistance in trypanosomas,” Parasitology (2013) 140:1478-1491. cited by applicant
Andrews, N. W. et al., “Adhesion and Interiorization of Trypanosoma cruzi in Mammalian Cells,” J. Protozool. (1982) 29(2):264-269. cited by applicant
Bartholomeu. D. C. et al., “Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi,” Nucleic Acids Research (2009) 37(10):3407-3417. cited by applicant
Bayer-Santos, E. et al., “Proteomic Analysis of Trypanosoma cruzi Secretome: Characterization of Two Populations of Extracellular Vesicles and Soluble Proteins,” Journal of Proteome Research (2013) 12:883-897. cited by applicant
Boari, J. T. et al., “IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi Infection by Recruiting Suppressive IL-10-Producing Neutrophils,” PLoS Pathog. (2012) 8(4).e1002658, 17 pages. cited by applicant
Boscardin. S. B. et al., “Chagas' disease: an update on immune mechanisms and therapeutic strategies.” J. Cell. Mol. Med. (2010) 14(6B):1373-1384. cited by applicant
Brener, Z, “Therapeutic Activity and Criterion of Cure on Mice Experimentally Infected with Trypanosoma Cruzi,” Rev. Inst. Med. trop. Sao Paulo (1962) 4(6):389-396. cited by applicant
Brodskyn, C. I. et al., “lgG subclasses responsible for immune clearance in mice infected with Tryaponosoma cruzi,” lmmunol. Cell Biol. (1989) 67:343-348. cited by applicant
Bryan, M.A. et al., “Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice,” PLoS Negl. Trop. Dis (2010) 4(7):e733, 16 pages. cited by applicant
Carod-Artal, F. J et al., “Chagas disease and stroke.” Lancent Neurol (2010) 9:533-542. cited by applicant
Cordeiro, F. D. et al., “Anti-Trypanosoma cruzi Immunoglobulin G1 can be a Useful Tool for Diagnosis and Prognosis of Human Chagas' Disease,” Clinical and Diagnostic Laboratory Immunology (2001) 8(1):112-118. cited by applicant
Cummings. K. L. et al., “Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR,” Molecular & Biochemical Parasitology (2003) 129:53-59. cited by applicant
Cunha-Neto, E. et al., “Myocardial gene and protein expression profiles after autoimmune injury in Chagas' disease cardiomyopathy,” Autoimmunity Reviews (2011) 10:163-165. cited by applicant
De Araujo, F. F. et al., “Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease,” PLoS Negl. Trop. Dis. (2011) 5(5):e992, 8 pages. cited by applicant
De Pablos. L. M. et al., “Differential Expression and Characterization of a Member of the Mucin-Associate Surface Protein Family Secreted by Trypanosoma cruzi,” Infection and Immunity (2011) 79(10):3993-4001. cited by applicant
De Pablos. L. M. et al.. “Multigene Families in Trypanosoma cruzi and their Role in Infectivity,” Infection and Immunity (2012) 80(7):2258-2264. cited by applicant
Dos Santos, S. L. et al., “The MASP Family of Trypanosoma cruzi: Changes in Gene Expression and Antigenic Profile during the Acute Phase of Experimental Infection,” PLoS Negl. Trop. Dis. (2012) 6(8):e1779, 14 pages. cited by applicant
El-Sayed. N. M. et al., “The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease,” Science (2005) 309:409-415. cited by applicant
Galväo Da Silva. A. P et al., “Resistant mice lacking interleukin-12 become susceptible to Trypanosoma cruzi infection but fail to mount a T helper type 2 response.” Immunology (2003) 108:230-237. cited by applicant
Gascon, J. et al., “Chagas disease in Spain, the United States and other non-endemic countries,” Acta Tropica (2010) 115:22-27. cited by applicant
Grauert, M. R. et al., “Trypanosoma cruzi infection enhances polyreactive antibody response in an acute case of human Chagas' disease,” Clin. Exp. lmmunol. (1993) 93:85-92. cited by applicant
Guedes, P MdM et al., “IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-induced Myocarditis,” PLoS Negl. Trop. Dis (2010) 4(2):efi04,11 pages. cited by applicant
Hoft, D. F. et al., “Involvement of CD4+ Th1 Cells in Systemic Immunity Protective against Primary and Secondary Challenges with Trypanosoma cruzi,” Infection and Immunity (2000) 68(1):197-204. cited by applicant
Hölscher, C. et al., “Tumor Necrosis Factor Alpha-Mediated Toxic Shock in Trypanosoma cruzi—⋅Infected Interleukin 10-Deficient Mice,” Infection and Immunity (2000) 68(7):4075-4083. cited by applicant
Hunter, C. A. et al.. “IL-10 is Required to Prevent Immune Hyperactivity During Infection with Trypanosoma cruzi,” The Journal of Immunology (1997) 158:3311-3316. cited by applicant
Jager, A. et al., “Th1 Th17, and Th9 Effector Celis induce Experimental Autoimmune Encephalomyelitis with Different Pathological Phenotypes,” The Journal of Immunology (2009) 183: 7169-7177. cited by applicant
Junqueira, C. et al., “The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease,” Expert Reviews in Molecular Medicine (2010) 12:e29, 23 pages. cited by applicant
Kierszenbaum, F., “Protection of Congenitally Athyrnic Mice Against Trypanosoma cruzi Infection by Passive Antibody Transfer,” J. Parasitol. (1980) 66(4):673-675. cited by applicant
Korn, T. et al., “IL-17 and Th17 Cells,” Annu. Rev. Immunol (2009) 27:485-517. cited by applicant
Kreth.I. A. U. et al., “Protective Effects of Specific Antibodies in Trypanosoma Cruzi Infections.” The Journal of Immunology (1976) 116(3):755-760. cited by applicant
Krettli, A U. et al., “Membrane-bound antibodies to bloodstream Trypanosoma cruzi in mice: strain differences in susceptibility to complement-mediated lysis,” Clin. Exp. Imrnunol. (1979) 37:416-423. cited by applicant
Krettli, A. U., “The utility of anti-trypomastigote lytic antibodies for determining cure of Ttypanosoma cruzi infections in treated patients: an overview and perspectives,” Mem Inst Oswaldo Cruz, Rio de Janeiro (2009) 104 (Suppl. 1):142-151. cited by applicant
Kumar, S. et al., “Antigen-Specific Th1 But Not Th2 Cells Provide Protection from Lethal Trypanosoma cruzi Infection in Mice,” The Journal of Immunology (2001) 166:4596-4603. cited by applicant
Kumar. S. et al., “The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi,” Parasite Immunology (1998) 20:207-216. cited by applicant
Lages Silva. E. et al., “Effective of protective and non-protective antibodies in the phagocytosis rate of Trypanosoma cruzi blood forms by mouse peritoneal macrophages,” Parasite Immunology {1987) 9:21-30. cited by applicant
Lee, B Y. et al., “Modeling the economic value of a Chagas' disease therapeutic vaccine,” Human Vaccines & Immunotherapeutics (2012) 8(9):1293-1301. cited by applicant
Lee, B. Y. et al., “Global economic burden of Chagas disease: a computational simulation model,” Lancet Infect. Dis (2013) 13(4):342-348. cited by applicant
Lima. E. C. S et al.. “Evidence for a Protective Role of Tumor Necrosis Factor in the Acute Phase of Trypanosoma cruzi infection in Mice,” Infection and Immunity (1997) 65(2):457-465. cited by applicant
Lima-Martins, M. V. C. et al., “Antibody-dependent cell cytotoxicity against Trypanosoma cruzi is only mediated by protective antibodies,” Parasite Immunology (1985) 7:367-376. cited by applicant
Magalhäes, L.M. D. et al., “High Interleukin 17 Expression ls Correlated with Better Cardiac Function in Human Chagas Disease.” The Journal of Infectious Diseases (2013) 207:661-665. cited by applicant
Michailowsky, V. et al., “Humoral and Cellular Immune Responses to Tryapnosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease,” Infection and Immunity (2003) 71(6): 3165-3171. cited by applicant
Michailowsky, V. et al., “Pivotal Role of Interleukin-12 and Interferon-y Axis in Controlling Tissue Parasitism and Inflammation in the Heart and Central Nervous System during Trypanosoma cruzi Infection,” American Journal of Pathology (2001) 159(5):1723-1733. cited by applicant
Miyazaki. Y. et al., “IL-17 ls Necessary for Host Protection against Acute-Phase Trypanosoma cruzi infection,” The Journal of Immunology (2010) 185:1150-1157. cited by applicant
Morrot, A. et al., “Dynamics of Lymphocyte Populations during Trypanosoma cruzi Infection: From Thymocyte Depletion to Differential Cell Expansion/Contraction in Peripheral Lymphoid Organs,” Journal of Tropical Medicine (2012) 2012(747185): 7 pages. cited by applicant
Murta, S. M. F. et al., “Differential gene expression in Trypanosom cruzi populations susceptible and resistant to benznidazole,” Acta Tropica (2008) 107:59-65. cited by applicant
Nakayasu, E. S. et al., “Improved Proteomic Approach for the Discovery of Potential Vaccine Targets in Trypanosoma cruzi,” Journal of Proteome Research (2012) 11:237-246. cited by applicant
Nielsen, M. et al., “Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method,” BMC Bioinformatics (2007) 8:238, 12 pages. cited by applicant
Nielsen. M. et al., “NN-align, An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction,” BMC Bioinformatics (2009) 10:296, 10 pages. cited by applicant
Okabe, K. et al., “Cell-Mediated Cytotoxicity to Trypanosoma cruzi,” Clinical Immunology and Immunopathology (1980) 16:344-353. cited by applicant
Pereira-Chioccola, V. L. et al., “Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-a-galactosyl antibodies,” Journal of Cell Science (1000) 113:1299-1307. cited by applicant
Perez, A. R. et al., “Extrathymic CD4+CD8+ lymphocytes in Chagas disease: possible relationship with an immunoendocrine imbalance,” Ann. N.Y. Acad. Sci. (2012) 1262:27-36. cited by applicant
Pinazom. J. et al., “Tolerance of Benznidazole in Treatment of Chagas' Disease in Adults,” Antimicrobial Agents and Chemotherapy (2010) 54(11):4896-4899. cited by applicant
Primavera. K. S. C. et al., “Chagas' Disease: lgA, lgM and IgG Antibodies to T. cruzi Amastigote, Trypomastigote and Epimastigote Antigens in Acute and in Different Chronic Forms of the Disease.” Rev. lnst. Med. Trop. Sao Paulo (1990) 32(3): 172-180. cited by applicant
Quijano-Hernandez, I. et al., “Advances and challenges toward a vaccine against Chagas disease.” Human Vaccines (2011) 7(11 ):1184-1191. cited by applicant
Rassi. Jr. A. et al., “America Trypanosomiasis (Chagas Disease),” Infect. Dis. Clin. N. Am. (2012) 26:275-291. cited by applicant
Rottenberg, M. E. et al., “Differential Susceptibilities of Mice Genomically Deleted of CD4 and CD8 to lnfections with Trypanosoma cruzi or Trypanosoma brucei,” Infection and Immunity (1993) 61(12):5129-5133. cited by applicant
Singh, H. et al., “ProPred: prediction of HLA-DR binding sites,” Bioinformatics (2001) 17(12): 1236-1237. cited by applicant
Singh. H. et al., “ProPred1: prediction of promiscuous MHC Class-1 binding sites,” Bioinfomatics (2003) 19(8):1009-1014. cited by applicant
Sturniolo. T et al., “Generation of tissue-specific and promiscuous HLA ligand databases using DNA rnicroarrays and virtual HLA class ll matrices,” Nature Biotechnology (1999) 17:555-561. cited by applicant
Takehara, H. A. et al., “A comparative study of anti-Trypanosoma cruzi serum obtained in acute and chronic phase of infection in mice,” Immunology Letters (1989/1990) 23:81-86. cited by applicant
Tarleton, R. L. et al., “Susceptibility of β2-rnicroglobulin-deficient mice to Trypanosoma cruzi infection,” Nature (1992) 356:338-340. cited by applicant
Tosello Boari, J. et al., “IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi infection by Recruiting Suppressive IL-10-Producing Neutrophils,” PLoS Pathog (2012) 8(4):e⋅1002658, 17 pages. cited by applicant
Travassos, L. R. et 31., “Carbohydrate immunity in American trypanosomiasis,” Splinter Semin Immunopathol (1993) 15: 183-204. cited by applicant
Vasconcelos, J. R. et al., “Protective Immunity Against Trypanosoma cruzi Infection in a Highly Susceptible Mouse Strain After Vaccination with Genes Encoding the Amastigote Surface Protein-2 and Trans-Sialidase,” Human Gene Therapy (2004) 15:878-886. cited by applicant
Vazquez-Chagoyan, J. C. et al, “Vaccine Development Against Trypanosoma cruzi and Chagas Disease,” Advances in Parasitology (2011) L. M. Weiss. H. B. Tanowitz, and L. V Kirchhoff (eds.) Burlington Academic Press, vol. 75. pp. 121-145. cited by applicant
Wang, P. et al, “A Systematic Assessment of MHC Class II Peptide Binding Predictions and Evaluation of a Consensus Approach,” PLoS Comput Biol (2008) 4(4):e1000048. 11 pages. cited by applicant
Wurster, A. L. et al., “Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL,” The Journal of Biological Chemistry (2002) 277(30):27169-27175. cited by applicant - Assistant Examiner: Jackson-Tongue, Lakia J
- Primary Examiner: Nickol, Gary B
- Attorney, Agent or Firm: Norton Rose Fulbright US LLP
- Accession Number: edspgr.10279023
- Patent Number:

Copyright © Department of Culture and Tourism, all rights reserved.
Copyright © 2024 Department of Culture and Tourism, all rights reserved. Powered By EBSCO Stacks 3.3.0 [353] | Staff Login
No Comments.