Development of Improved Vaccine Adjuvants Based on the Saponin Natural Product QS-21 through Chemical Synthesis

Accounts of Chemical Research

Volumn 49, Issue 9, 2016, Pages 1741-1756

  Fernández Tejada, Alberto ^a   Tan, Derek S ^a   Gin, David Y ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUORESCENT DYE; IMMUNOLOGICAL ADJUVANT; RADIOACTIVE IODINE; SAPONIN; SAPONIN QA-21V1;

ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; MOUSE; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; FLUORESCENT DYES; IODINE RADIOISOTOPES; MICE; MOLECULAR STRUCTURE; SAPONINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84988484489     PISSN: 00014842     EISSN: 15204898     Source Type: Journal    
DOI: 10.1021/acs.accounts.6b00242     Document Type: Article

References (40)

1. Jones, L. H. Recent Advances in the Molecular Design of Synthetic Vaccines Nat. Chem. 2015, 7, 952-960 10.1038/nchem.2396
2. Reed, S. G.; Orr, M. T.; Fox, C. B. Key Roles of Adjuvants in Modern Vaccines Nat. Med. 2013, 19, 1597-1608 10.1038/nm.3409
3. HogenEsch, H. Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants Front. Immunol. 2013, 3, 406 10.3389/fimmu.2012.00406
4. Fox, C. B.; Haensler, J. An Update on Safety and Immunogenicity of Vaccines Containing Emulsion-based Adjuvants Expert Rev. Vaccines 2013, 12, 747-758 10.1586/14760584.2013.811188
5. O'Hagan, D. T.; Fox, C. B. New Generation Adjuvants-from Empiricism to Rational Design Vaccine 2015, 33 (Suppl 2) B14-20 10.1016/j.vaccine.2015.01.088
6. Ragupathi, G.; Gardner, J. R.; Livingston, P. O.; Gin, D. Y. Natural and Synthetic Saponin Adjuvant QS-21 for Vaccines against Cancer Expert Rev. Vaccines 2011, 10, 463-470 10.1586/erv.11.18
7. Alving, C. R.; Peachman, K. K.; Rao, M.; Reed, S. G. Adjuvants for Human Vaccines Curr. Opin. Immunol. 2012, 24, 310-315 10.1016/j.coi.2012.03.008
8. Hu, J.; Qiu, L.; Wang, X.; Zou, X.; Lu, M.; Yin, J. Carbohydrate-based Vaccine Adjuvants-Discovery and Development Expert Opin. Drug Discovery 2015, 10, 1133-1144 10.1517/17460441.2015.1067198
9. Marciani, D. J. A Retrospective Analysis of the Alzheimer's Disease-The Critical Need for New Development Strategies J. Neurochem. 2016, 137, 687-700 10.1111/jnc.13608
10. Kensil, C. R.; Patel, U.; Lennick, M.; Marciani, D. Separation and Characterization of Saponins with Adjuvant Activity from Quillaja Saponaria Molina Cortex J. Immunol. 1991, 146, 431-437
11. Soltysik, S.; Bedore, D. A.; Kensil, C. R. Adjuvant Activity of QS-21 Isomers Ann. N. Y. Acad. Sci. 1993, 690, 392-395 10.1111/j.1749-6632.1993.tb44041.x
12. Cleland, J. L.; Kensil, C. R.; Lim, A.; Jacobsen, N. E.; Basa, L.; Spellman, M.; Wheeler, D. A.; Wu, J.-Y.; Powell, M. F. The Isomerization and Formulation Stability of the Vaccine Adjuvant QS-21 J. Pharm. Sci. 1996, 85, 22-28 10.1021/js9503136
13. Petrovsky, N.; Cooper, P. D. Carbohydrate-based Immune Adjuvants Expert Rev. Vaccines 2011, 10, 523-537 10.1586/erv.11.30
14. Pink, J. R.; Kieny, M.-P. 4th Meeting on Novel Adjuvants Currently in/close to Human Clinical Testing, World Health Organization Vaccine 2004, 22, 2097-2102 10.1016/j.vaccine.2004.01.021
15. Kensil, C. R. Saponins as Vaccine Adjuvants Crit. Rev. Ther. Drug Carrier Syst. 1996, 13, 1-55
16. Marciani, D. J. Vaccine Adjuvants: Role and Mechanisms of Action in Vaccine Immunogenicity Drug Discovery Today 2003, 8, 934-943 10.1016/S1359-6446(03)02864-2
17. Soltysik, S.; Wu, J.-Y.; Recchia, J.; Wheeler, D. A.; Newman, M. J.; Coughlin, R. T.; Kensil, C. R. Structure/function Studies of QS-21 Adjuvant: Assessment of Triterpene Aldehyde and Glucuronic Acid Roles in Adjuvant Function Vaccine 1995, 13, 1403-1410 10.1016/0264-410X(95)00077-E
18. Marty-Roix, R.; Vladimer, G. I.; Pouliot, K.; Weng, D.; Buglione-Corbett, R.; West, K.; MacMicking, J. D.; Chee, J. D.; Wang, S.; Lu, S.; Lien, E. Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants J. Biol. Chem. 2016, 291, 1123-1136 10.1074/jbc.M115.683011
19. Marciani, D. J.; Press, J. B.; Reynolds, R. C.; Pathak, A. K.; Pathak, V.; Gundy, L. E.; Farmer, J. T.; Koratich, M. S.; May, R. D. Development of Semisynthetic Triterpenoid Saponin Derivatives with Immune Stimulating Activity Vaccine 2000, 18, 3141-3151 10.1016/S0264-410X(00)00118-3
20. Wang, P.; Dai, Q.; Thogaripally, P.; Zhang, P.; Michalek, S. M. Synthesis of QS-21-based Immunoadjuvants J. Org. Chem. 2013, 78, 11525-11534 10.1021/jo402118j
21. Kim, Y. J.; Gin, D. Y. Synthesis of the Trisaccharide Portion of the Immunological Adjuvant QS-21A via Sulfonium-mediated Oxidative and Dehydrative Glycosylation Org. Lett. 2001, 3, 1801-1804 10.1021/ol015651u
22. Zhu, X.; Yu, B.; Hui, Y.; Schmidt, R. R. Synthesis of the Trisaccharide and Tetrasaccharide Moieties of the Potent Immunoadjuvant QS-21 Eur. J. Org. Chem. 2004, 2004, 965-973 10.1002/ejoc.200300580
23. Zhu, X.; Yu, B.; Hui, Y.; Higuchi, R.; Kusano, T.; Miyamoto, T. Synthesis and Absolute Stereochemistry of the Acyl Moiety of Quillaja Saponins Tetrahedron Lett. 2000, 41, 717-719 10.1016/S0040-4039(99)02124-3
24. Wang, P.; Kim, Y. J.; Navarro-Villalobos, M.; Rohde, B. D.; Gin, D. Y. Synthesis of the Potent Immunostimulatory Adjuvant QS-21A J. Am. Chem. Soc. 2005, 127, 3256-3257 10.1021/ja0422007
25. Kim, Y. J.; Wang, P.; Navarro-Villalobos, M.; Rohde, B. D.; Derryberry, J.; Gin, D. Y. Synthetic Studies of Complex Immunostimulants from Quillaja Saponaria: Synthesis of the Potent Clinical Immunoadjuvant QS-21Aapi J. Am. Chem. Soc. 2006, 128, 11906-11915 10.1021/ja062364i
26. Deng, K.; Adams, M. M.; Damani, P.; Livingston, P. O.; Ragupathi, G.; Gin, D. Y. Synthesis of QS-21-Xylose: Establishment of the Immunopotentiating Activity of Synthetic QS-21 Adjuvant with a Melanoma Vaccine Angew. Chem., Int. Ed. 2008, 47, 6395-6398 10.1002/anie.200801885
27. Ragupathi, G.; Damani, P.; Deng, K.; Adams, M. M.; Hang, J.; George, C.; Livingston, P. O.; Gin, D. Y. Preclinical Evaluation of the Synthetic Adjuvant SQS-21 and its Constituent Isomeric Saponins Vaccine 2010, 28, 4260-4267 10.1016/j.vaccine.2010.04.034
28. Deng, K.; Adams, M. M.; Gin, D. Y. Synthesis and Structure Verification of the Vaccine Adjuvant QS-7-Api. Synthetic Access to Homogeneous Quillaja Saponaria Immunostimulants J. Am. Chem. Soc. 2008, 130, 5860-5861 10.1021/ja801008m
29. Adams, M. M.; Damani, P.; Perl, N. R.; Won, A.; Hong, F.; Livingston, P. O.; Ragupathi, G.; Gin, D. Y. Design and Synthesis of Potent Quillaja Saponin Vaccine Adjuvants J. Am. Chem. Soc. 2010, 132, 1939-1945 10.1021/ja9082842
30. Garcia, B. A.; Poole, J. L.; Gin, D. Y. Direct Glycosylations with 1-Hydroxy Glycosyl Donors Using Trifluoromethanesulfonic Anhydride and Diphenyl Sulfoxide J. Am. Chem. Soc. 1997, 119, 7597-7598 10.1021/ja971067y
31. Chea, E. K.; Fernández-Tejada, A.; Damani, P.; Adams, M. M.; Gardner, J. R.; Livingston, P. O.; Ragupathi, G.; Gin, D. Y. Synthesis and Preclinical Evaluation of QS-21 Variants Leading to Simplified Vaccine Adjuvants and Mechanistic Probes J. Am. Chem. Soc. 2012, 134, 13448-13457 10.1021/ja305121q
32. Walkowicz, W. E.; Fernández-Tejada, A.; George, C.; Corzana, F.; Jiménez-Barbero, J.; Ragupathi, G.; Tan, D. S.; Gin, D. Y. Quillaja Saponin Variants with Central Glycosidic Linkage Modifications Exhibit Distinct Conformations and Adjuvant Activities Chem. Sci. 2016, 7, 2371-2380 10.1039/C5SC02978C
33. Fernández-Tejada, A.; Chea, E. K.; George, C.; Pillarsetty, N.; Gardner, J. R.; Livingston, P. O.; Ragupathi, G.; Lewis, J. S.; Tan, D. S.; Gin, D. Y. Development of a Minimal Saponin Vaccine Adjuvant Based on QS-21 Nat. Chem. 2014, 6, 635-643 10.1038/nchem.1963
34. Nico, D.; Santos, F. N.; Borja-Cabrera, G. P.; Palatnik, M.; Palatnik de Sousa, C. B. Assessment of the Monoterpene, Glycidic and Triterpene-moieties' Contributions to the Adjuvant Function of the CP05 Saponin of Calliandra Pulcherrima Benth During Vaccination Against Experimental Visceral Leishmaniasis Vaccine 2007, 25, 649-658 10.1016/j.vaccine.2006.08.035
35. Oda, K.; Matsuda, H.; Murakami, T.; Katayama, S.; Ohgitani, T.; Yoshikawa, M. Adjuvant and Haemolytic Activities of 47 Saponins Derived from Medicinal and Food Plants Biol. Chem. 2000, 381, 67-74 10.1515/BC.2000.009
36. + T Cells J. Immunol. 2011, 187, 55-63 10.4049/jimmunol.1004114
37. Scott, M. T.; Goss-Sampson, M.; Bomford, R. Adjuvant Activity of Saponin: Antigen Localization Studies Int. Arch. Allergy Immunol. 2004, 77, 409-412 10.1159/000233817
38. Rhodes, J. Discovery of Immunopotentiatory Drugs: Current and Future Strategies Clin. Exp. Immunol. 2002, 130, 363-369 10.1046/j.1365-2249.2002.02016.x
39. Fernández-Tejada, A.; Chea, E. K.; George, C.; Gardner, J. R.; Livingston, P. O.; Ragupathi, G.; Tan, D. S.; Gin, D. Y. Design, Synthesis, and Immunologic Evaluation of Vaccine Adjuvant Conjugates Based on QS-21 and Tucaresol Bioorg. Med. Chem. 2014, 22, 5917-5923 10.1016/j.bmc.2014.09.016
40. Fernández-Tejada, A.; Tan, D. S.; Gin, D. Y. Versatile Strategy for the Divergent Synthesis of Linear Oligosaccharide Domain Variants of Quillaja Saponin Vaccine Adjuvants Chem. Commun. 2015, 51, 13949-13952 10.1039/C5CC05244K