Rational Vaccine Design: Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Cristina Nativi.

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. 

  • vaccine
  • design
  • antigen
Please wait, diff process is still running!

References

  1. Zhu, Y.; An, X.; Zhang, X.; Qiao, Y.; Zheng, T.; Li, X. STING: A master regulator in the cancer-immunity cycle. Mol. Cancer 2019, 18, 1–15.
  2. Pulendran, B.; Li, S.; Nakaya, H.I. Systems Vaccinology. Immunity 2010, 33, 516–529.
  3. Rappuoli, R. Bridging the knowledge gaps in vaccine design. Nat. Biotechnol. 2007, 25, 1361–1366.
  4. Brodin, P.; Jojic, V.; Gao, T.; Bhattacharya, S.; Angel, C.J.L.; Furman, D.; Shen-Orr, S.; Dekker, C.L.; Swan, G.E.; Butte, A.J.; et al. Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences. Cell 2015, 160, 37–47.
  5. Cheung, P.; Vallania, F.; Warsinske, H.C.; Donato, M.; Schaffert, S.; Chang, S.E.; Dvorak, M.; Dekker, C.L.; Davis, M.M.; Utz, P.J.; et al. Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 2018, 173, 1385–1397.e14.
  6. Hagan, T.; Cortese, M.; Rouphael, N.; Boudreau, C.; Linde, C.; Maddur, M.S.; Das, J.; Wang, H.; Guthmiller, J.; Zheng, N.-Y.; et al. Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans. Cell 2019, 178, 1313–1328.e13.
  7. Cortese, M.; Sherman, A.C.; Rouphael, N.G.; Pulendran, B. Systems Biological Analysis of Immune Response to Influenza Vaccination. Cold Spring Harb. Perspect. Med. 2020, a038596.
  8. Chaussabel, D.; Quinn, C.; Shen, J.; Patel, P.; Glaser, C.; Baldwin, N.; Stichweh, D.; Blankenship, D.; Li, L.; Munagala, I.; et al. A modu-lar analysis framework for blood genomics studies: Application to systemic lupus erythematosus. Immunity 2008, 29, 150–164.
  9. Li, S.; Rouphael, N.; Duraisingham, S.S.; Romero-Steiner, S.; Presnell, S.R.; Davis, C.; Schmidt, D.S.; E Johnson, S.; Milton, A.; Rajam, G.; et al. Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat. Immunol. 2014, 15, 195–204.
  10. Wimmers, F.; Pulendran, B. Emerging technologies for systems vaccinology—Multiomics integration and single-cell (epi)genomic profiling. Curr. Opin. Immunol. 2020, 65, 57–64.
  11. Li, S.; Sullivan, N.L.; Rouphael, N.; Yu, T.; Banton, S.; Maddur, M.S.; McCausland, M.; Chiu, C.; Canniff, J.; Dubey, S.; et al. Metabolic Phenotypes of Response to Vaccination in Humans. Cell 2017, 169, 862–877.e17.
  12. Braun, R.O.; Brunner, L.; Wyler, K.; Auray, G.; Garcia-Nicolas, O.; Python, S.; Zumkehr, B.; Gaschen, V.; Stoffel, M.H.; Collin, N.; et al. System immunology-based identification of blood transcrip-tional modules correlating to antibody responses in sheep. NPJ Vaccines 2018, 3, 41.
  13. Matthijs, A.M.F.; Auray, G.; Jakob, V.; Garcia-Nicolas, O.; Braun, R.O.; Keller, I.; Bruggman, R.; Devriendt, B.; Boyen, F.; Guzman, C.A.; et al. Systems Immu-nology Characterization of Novel Vaccine Formulations for Mycoplasma hyopneumoniae Bacterins. Front. Immunol. 2019, 10, 1087.
  14. Tsang, J.S.; Dobaño, C.; VanDamme, P.; Moncunill, G.; Marchant, A.; Ben Othman, R.; Sadarangani, M.; Koff, W.C.; Kollmann, T.R. Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome? Trends Immunol. 2020, 41, 457–465.
  15. Delany, I.; Rappuoli, R.; Seilb, K.L. Vaccines, reverse vaccinology and bacterial pathogenesis. CSH Perspect. 2013, 3, a012476.
  16. Jefferies, J.M.C.; Macdonald, E.; Faust, S.N. Clarke SC, 13-valent pneumococcal conjugate vaccine (PCV13). Hum. Vaccines 2011, 7, 1012–1018.
  17. Rappuoli, R.; Bottomley, M.J.; D’Oro, U.; Finco, O.; De Gregorio, E. Reverse vaccinology 2.0: Human immunology instructs vac-cine antigen design. J. Exp. Med. 2016, 213, 469–481.
  18. Burton, D.R. What Are the Most Powerful Immunogen Design Vaccine Strategies? Reverse Vaccinology 2.0 Shows Great Promise. Cold Spring Harb. Perspect. Biol. 2017, 9, 030262.
  19. Correia, B.E.; Bates, J.T.; Loomis, R.J.; Baneyx, G.; Carrico, C.; Jardine, J.G.; Rupert, P.B.; Correnti, C.; Kalyuzhniy, O.; Vittal, V.; et al. Proof of principle for epitope-focused vaccine design. Nat. Cell Biol. 2014, 507, 201–206.
  20. Graham, B.S.; Gilman, M.S.A.; McLellan, J.S. Structure-Based Vaccine Antigen Design. Annu. Rev. Med. 2019, 70, 91–104.
  21. Anasir, M.A. Chit Laa Poh. Structural Vaccinology for Viral Vaccine Design. Front Microbiol. 2019, 10, 738.
  22. Malonis, R.J.; Lai, J.R.; Vergnolle, O. Peptide-Based Vaccines: Current Progress and Future Challenges. Chem. Rev. 2020, 120, 3210–3229.
  23. Alam, S.M.; Dennison, S.M.; Aussedat, B.; Vohra, Y.; Park, P.K.; Fernández-Tejada, A.; Stewart, S.; Jaeger, F.H.; Anasti, K.; Blinn, J.H.; et al. Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc. Natl. Acad. Sci. USA 2013, 110, 18214–18219.
  24. Kanekiyo, M.; Ellis, D.; King, N.P. New Vaccine Design and Delivery Technologies. J. Infect. Dis. 2019, 219, S88–S96.
  25. Compañón, I.; Guerreiro, A.; Mangini, V.; Castro-López, J.; Escudero-Casao, M.; Avenoza, A.; Busto, J.H.; Castillón, S.; Jiménez-Barbero, J.; Asensio, J.L.; et al. Structure-based design of potent tumor-associated antigens: Modulation of peptide presentation by single-atom O/S or O/Se substitutions at the glycosidic linkage. J. Am. Chem. Soc. 2019, 141, 4063–4072.
  26. Lewis, G.K.; DeVico, A.L.; Gallo, R.C. Antibody persistence and T cell balance: Two key factors confronting HIV vaccine development. Proc. Natl. Acad. Sci. USA 2014, 111, 15614.
  27. Joyce, M.G.; Zhang, B.; Ou, L.; Chen, M.; Chuang, G.-Y.; Druz, A.; Kong, W.-P.; Lai, Y.-T.; Rundlet, E.J.; Tsybovsky, Y.; et al. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat. Struct. Mol. Biol. 2016, 23, 811–820.
  28. Ngwuta, J.O.; Chen, M.; Modjarrad, K.; Joyce, M.G.; Kanekiyo, M.; Kumar, A.; Yassine, H.M.; Moin, S.M.; Killikelly, A.M.; Chuang, G.-Y.; et al. Prefusion F–specific antibodies determine the magnitude of RSV neutralizing activity in human sera. Sci. Transl. Med. 2015, 7, 309ra162.
  29. Pizza, M.; Scarlato, V.; Masignani, V.; Giuliani, M.M.; Arico, B.; Comanducci, M.; Jennings, G.T.; Baldi, L.; Bartolini, E.; Capec-chi, B.; et al. Identification of vaccine candidates against serogroup B meningococ-cus by whole-genome sequencing. Science 2000, 287, 1816–1820.
  30. Hollingshead, S.; Jongerius, I.; Exley, R.M.; Johnson, S.; Lea, S.M.; Tang, C.M. Structure-based design of chimeric antigens for multivalent protein vaccines. Nat. Commun. 2018, 9, 1–10.
  31. Geldmacher, A.; Freier, A.; Losch, F.O.; Walden, P. Therapeutic vaccination for cancer immunotherapy: Antigen selection and clinical response. Human Vaccines 2011, 7, 115.
  32. Butterfield, L.H. Lessons learned from cancer vaccine trials and target antigen choice. Cancer Immunol. Immunother. 2016, 65, 805–812.
  33. Xu, Z.; Kulp, D.W. Protein engineering and particulate display of B-cell epitopes to facilitate development of novel vaccines. Curr. Opin. Immunol. 2019, 59, 49.
  34. Cheever, M.A.; Allison, J.P.; Ferris, A.S.; Finn, O.J.; Hastings, B.M.; Hecht, T.T.; Mellman, I.; Prindiville, S.A.; Steinman, R.M.; Viner, J.L.; et al. The prioritization of cancer an-tigens: A national cancer institute pilot project for the acceleration of translational research Clin. Cancer Res 2009, 15, 5323.
  35. Radford, K.J.; Caminschi, I. New generation of dendritic cell vaccines. Hum. Vaccines Immunother. 2013, 9, 259–264.
  36. Srivastava, S.; Sharma, S.K.; Srivastava, V.; Kumar, A. Proteomic Exploration of Listeria monocytogenes for the Purpose of Vaccine Designing Using a Reverse Vaccinology Approach. Int. J. Pept. Res. Ther. 2021, 27, 779–799.
  37. Calderon-Gonzalez, R.; Tobes, R.; Pareja, E.; Frande-Cabanes, E.; Petrovsky, N.; Alvarez-Dominguez, C. Identification and characterisation of T cell epitopes for incorporation into dendritic cell-delivered Listeria vaccines. J. Immunol. Methods 2015, 424, 111–119.
  38. Kono, M.; Nakamura, Y.; Suda, T.; Uchijima, M.; Tsujimura, K.; Nagata, T.; Giermasz, A.S.; Kalinski, P.; Nakamura, H.; Chida, K. En-hancement of protective immunity against intracellular bacteria using type-1 polarized dendritic cell (DC) vaccine. Vaccine 2012, 30, 2633–2639.
  39. Calderon-Gonzalez, R.; Frande-Cabanes EBronchalo-Vicente, L.; Lecea-Cuello, M.J.; Bosch-Martinez, A.; Fanarraga, M.L.; Yañez-Diaz, S.; Carrasco-Marin, E.; Alvarez-Dominguez, C. Cellular vaccines in listeriosis: Role of the Listeria antigen GAPDH. Front. Cell. Infect. Microbiol. 2014, 4, 22.
  40. Alvarez-Dominguez, C.; Salcines-Cuevas, D.; Teran-Navarro, H.; Calderon-Gonzalez, R.; Tober, R.; Garcia, I.; Grijalvo, S.; Paradela, A.; Seoane, A.; Sangari, F.J.; et al. Epitopes for multivalent vaccines against Listeria, Mycobacterium and Streptococcus spp: A novel role for glyceraldehyde-3-phosphate dehydrogenase. Front. Cell. Infect. Microbiol. 2020, 10, 573348.
  41. Robbins, A. Progress towards vaccines we need and do not have. Lancet 1990, 335, 1436–1438.
  42. Brown, F.; Dougan GMoey, E.M. A short history of vaccination. In Vaccine Design; Brown, F., Dougan, G., Moey, E.M., Eds.; John Wiley and Sons: Chichester, UK, 1993; pp. 1–6.
  43. Schijns, V.E. Immunological concepts of vaccine adjuvant activity. Curr. Opin. Immunol. 2020, 12, 456–463.
  44. Christensen, D. Vaccine adjuvants: Why and how. Hum. Vaccines Immunother. 2016, 12, 2709–2711.
  45. Del Giudice, G.; Rappuoli, R.; Didierlaurent, A.M. Correlates of adjuvanticity: A review on adjuvants in licensed vaccines. Semin. Immunol. 2018, 39, 14–21.
  46. O’Hagan, D.T.; Fox, C.B. New generation adjuvants—From empiricism to rational design. Vaccine 2015, 33, B14–B20.
  47. Ribeiro, C.M.; Schijns, V.E. Immunology of Vaccine Adjuvants. In Methods in Molecular Biology; Springer International Publishing: New York, NY, USA, 2009; Volume 626, pp. 1–14.
  48. Shi, S.; Zhu, H.; Xia, X.; Liang, Z.; Ma, X.; Sun, B. Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity. Vaccine 2019, 37, 3167–3178.
  49. Bonam, S.R.; Partidos, C.D.; Halmuthur, S.K.M.; Muller, S. An overview of novel adjuvants designed for improving vaccine efficacy. Trends Pharmacol. Sci. 2017, 38, 771–793.
  50. Rueckert, C.; Guzmán, C.A. Vaccines: From empirical development to rational design. PLoS Pathog. 2012, 8, e1003001.
  51. Garçon, N.; Chomez, P.; Van Mechelen, M. GlaxoSmithKline Adjuvant Systems in vaccines: Concepts, achievements and perspectives. Expert Rev. Vaccines 2007, 6, 723–739.
  52. Pedersen, G.K.; Andersen, P.; Christensen, D. Immunocorrelates of CAF family adjuvants. Semin. Immunol. 2018, 39, 4–13.
  53. Molinaro, A.; Holst, O.; Di Lorenzo, F.; Callaghan, M.; Nurisso, A.; D’Errico, G.; Zamyatina, A.; Peri, F.; Berisio, R.; Jerala, R.; et al. Chemistry of Lipid A: At the Heart of Innate Immunity. Chem. Eur. J. 2015, 21, 500–519.
  54. Iwasaki, A.; Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 2004, 5, 987–995.
  55. Schromm, A.B.; Brandenburg, K.; Loppnow, H.; Moran, A.P.; Koch, M.H.J.; Rietschel, E.T.; Seydel, U. Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion. FEBS J. 2000, 267, 2008–2013.
  56. Kong, Q.; Six, D.A.; Liu, Q.; Gu, L.; Wang, S.; Alamuri, P.; Raetz, C.R.H.; Curtiss, R. Phosphate groups of lipid A are essential for Salmonella enterica serovar Typhimurium virulence and affect innate and adaptive immunity. Infect. Immun. 2012, 80, 3215–3224.
  57. Bhat, U.R.; Forsberg, L.S.; Carlson, R.W. Structure of lipid A component of Rhizobium leguminosarum bv. phaseoli lipopolysaccharide. Unique nonphosphorylated lipid A containing 2-amino- 2-deoxygluconate, galacturonate, and glu-cosamine. J. Biol. Chem. 1994, 269, 14402–14410.
  58. Raetz, C.R.H.; Reynolds, C.M.; Trent, M.S.; Bishop, R.E. Lipid A modification systems in Gram-negative bacteria. Annu. Rev. Biochem 2007, 76, 295–329.
  59. Plotz, B.M.; Lindner, B.; Stetter, K.O.; Holst, O. Characterization of a Novel Lipid A Containing D-Galacturonic Acid That Replaces Phosphate Residues. J. Biol. Chem. 2000, 275, 11222–11228.
  60. Silipo, A.; Vitiello, G.; Gully, D.; Sturiale, L.; Chaintreuil, C.; Fardoux, J.; Gargani, D.; Lee, H.I.; Kulkarni, G.; Busset, N.; et al. Covalently linked hopanoid-lipid A improves outer-membrane resistance of a Bradyrhizobium symbiont of legumes. Nat. Commun. 2014, 5, 5106.
  61. Di Lorenzo, F.; Pither, M.D.; Martufi, M.; Scarinci, I.; Guzmán-Caldentey, J.; Łakomiec, E.; Jachymek, W.; Bruijns, S.C.M.; Santamaría, S.M.; Frick, J.-S.; et al. Pairing Bacteroides vulgatus LPS Structure with Its Immunomodulatory Effects on Human Cellular Models. ACS Cent. Sci. 2020, 6, 1602–1616.
  62. Schwudke, D.; Linscheid, M.; Strauch, E.; Appel, B.; Zahringer, U.; Moll, H.; Muller, M.; Brecker, L.; Gronow, S.; Lindner, B. The Obligate Predatory Bdellovibrio bacteriovorus Possesses a Neutral Lipid A Containing α-D-Mannoses That Replace Phosphate Residues. J. Biol. Chem. 2003, 278, 27502–27512.
  63. Zhou, Z.; Ribeiro, A.A.; Lin, S.; Cotter, R.J.; Miller, S.I.; Raetz, C.R.H. Lipid A Modifications in Polymyxin-resistant Salmonella typhimurium. PRMA dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation. J. Biol. Chem. 2001, 276, 43111–43121.
  64. Silipo, A.; Molinaro, A.; Cescutti, P.; Bedini, E.; Rizzo, R.; Parrilli, M.; Lanzetta, R. Complete structural characterization of the lipid A fraction of a clinical strain of B. cepacia genomovar I lipopolysaccharide. Glycobiology 2005, 15, 561–570.
  65. Casabuono, A.C.; Czibener, C.; del Giudice, M.G.; Valguarnera, E.; Ugalde, J.E.; Couto, A.S. New Features in the Lipid A Structure of Brucella suis and Brucella abortus Lipopolysaccharide. J. Am. Chem. Soc. Mass. Spec. 2017, 28, 2716–2723.
  66. Zahringer, U.; Lindner, B.; Knirel, Y.A.; van den Akker, W.M.R.; Hiestand, R.; Heine, H.; Dehio, C. Structure and Biological Activity of the Short-chain Lipopolysaccharide from Bartonella henselae ATCC 49882T. J. Biol. Chem. 2004, 279, 21046–21054.
  67. Di Lorenzo, F.; de Castro, C.; Silipo, A.; Molinaro, A. Lipopolysaccharide structures of Gram-negative populations in the gut microbiota and effects on host interactions. FEMS Microbiol. Rev. 2019, 43, 257–272.
  68. Van Vliet, S.J.; Steeghs, L.; Bruijns, S.C.M.; Vaezirad, M.M.; Blok, C.S.; Busto, J.A.A.; Deken, M.; van Putten, J.P.M.; van Kooyk, Y. Variation of Neisseria gonorrhoeae Lipooligosaccharide Directs Dendritic Cell–Induced T Helper Responses. PLoS Pathog. 2009, 5, e1000625.
  69. Hagar, J.A.; Powell, D.A.; Aachoui, Y.; Ernst, R.K.; Miao, E.A. Cytoplasmic LPS activates caspase-11: Implications in TLR4-independent endotoxic shock. Science 2013, 341, 1250–1253.
  70. Kayagaki, N.; Wong, M.T.; Stowe, I.B.; Ramani, S.R.; Gonzalez, L.C.; Akashi-Takamura, S.; Miyake, K.; Zhang, J.; Lee, W.P.; Muszýnski, A.; et al. Noncanonical inflammasome activation by intracellular LPS in-dependent of TLR4. Science 2013, 341, 1246–1249.
  71. Shi, J.; Zhao, Y.; Wang, Y.; Gao, W.; Ding, J.; Li, P.; Hu, L.; Shao, F. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 2014, 514, 187–192.
  72. Viganò, E.; Diamond, C.E.; Spreafico, R.; Balachander, A.; Sobota, R.M.; Mortellaro, A. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat. Commun. 2015, 6, 8761.
  73. Chavarría-Velázquez, C.O.; Torres-Martínez, A.C.; Montaño, L.F.; Rendón-Huerta, E.P. TLR2 activation induced by H. pylori LPS promotes the differential expression of claudin-4, -6, -7 and -9 via either STAT3 and ERK1/2 in AGS cells. Immunobiology 2018, 223, 38–48.
  74. Jamalan, M.; Ardestani, S.K.; Zeinali, M.; Mosaveri, N.; Taheri, M.M. Effectiveness of Brucella abortus lipopol-ysaccharide as an adjuvant for tuberculin PPD. Biologicals 2011, 39, 23–28.
  75. Kianmehr, Z.; Soleimanjahi, H.; Ardestani, S.K.; Fotouhi, F.; Abdoli, A. Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice. Med. Microbiol. Immunol. 2015, 204, 205–213.
  76. Chilton, P.M.; Hadel, D.M.; To, T.T.; Mitchell, T.C.; Darveau, R.P. Adjuvant activity of naturally occurring monophos-phoryl lipopolysaccharide preparations from mucosa-associated bacteria. Infect. Immun. 2013, 81, 3317–3325.
  77. Ko, A.; Wui, S.R.; Ryu, J.I.; Do, H.T.T.; Lee, Y.J.; Lim, S.J.; Rhee, I.; Jung, D.I.; Park, J.-A.; Choi, J.-A.; et al. Comparison of the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide on Japanese encephalitis vaccine in mice. Arch. Pharmacal Res. 2018, 41, 219–228.
  78. Casella, C.; Mitchell, T. Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell. Mol. Life Sci. 2008, 65, 3231–3240.
  79. Embry, C.A.; Franchi, L.; Nunez, G.; Mitchell, T.C. Mechanism of Impaired NLRP3 Inflammasome Priming by Mono-phosphoryl Lipid A. Sci. Signal. 2011, 4, ra28.
  80. Casella, C.R.; Mitchell, T.C. Inefficient TLR4/MD-2 Heterotetramerization by Monophosphoryl Lipid A. PLoS ONE 2013, 8, e62622.
  81. Tanimura, N.; Saitoh, S.-I.; Ohto, U.; Akashi-Takamura, S.; Fujimoto, Y.; Fukase, K.; Shimizu, T.; Miyake, K. The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane. Int. Immunol. 2014, 26, 307–314.
  82. Pantel, A.; Cheong, C.; Dandamudi, D.; Shrestha, E.; Mehandru, S.; Brane, L.; Ruane, D.; Teixeira, A.; Bozzacco, L.; Steinman, R.M.; et al. A new synthetic TLR4 agonist, GLA, allows dendritic cells targeted with antigen to elicit Th1 T cell immunity in vivo. Eur. J. Immunol. 2012, 42, 101–109.
  83. Carter, D.; Fox, C.B.; Day, T.A.; Guderian, J.A.; Liang, H.; Rolf, T.; Vergara, J.; Sagawa, Z.K.; Ireton, G.; Orr, M.T.; et al. A structure-function approach to optimizing TLR4 ligands for human vaccines. Clin. Transl. Immunol. 2016, 5, e108.
  84. Gregg, K.A.; Harberts, E.; Gardner, F.M.; Pelletier, M.R.; Cayatte, C.; Yu, L.; McCarthy, M.P.; Marshall, J.D.; Ernst, R.K. Rationally designed TLR4 ligands for vaccine adjuvant discovery. mBio 2017, 8, e00492-17.
  85. Johnson, D. Synthetic TLR4-active Glycolipids as Vaccine Adjuvants and Stand-alone Immunotherapeutics. Curr. Top. Med. Chem. 2008, 8, 64–79.
  86. Khalaf, J.K.; Bowen, W.S.; Bazin, H.G.; Ryter, K.T.; Livesay, M.T.; Ward, J.R.; Evans, J.T.; Johnson, D.A. Characterization of TRIF selectivity in the AGP class of lipid A mimetics: Role of secondary lipid chains. Bioorg. Med. Chem. Lett 2015, 25, 547–553.
  87. Jiang, Z.H.; Budzynski, W.A.; Skeels, L.N.; Krantz, M.J.; Koganty, R.R. Novel lipid A mimetics derived from pentae-rythritol: Synthesis and their potent agonistic activity. Tetrahedron 2002, 58, 8833–8842.
  88. Akamatsu, M.; Fujimoto, Y.; Kataoka, M.; Suda, Y.; Kusumoto, S.; Fukase, K. Synthesis of lipid A monosaccharide ana-logues containing acidic amino acid: Exploring the structural basis for the endotoxic and antagonistic activities. Bioorg. Med. Chem. 2006, 14, 6759–6777.
  89. Ishizaka, S.T.; Hawkins, L.D. E6020: A synthetic Toll-like receptor 4 agonist as a vaccine adjuvant. Expert Rev. Vaccines 2007, 6, 773–784.
  90. Morefield, G.L.; Hawkins, L.D.; Ishizaka, S.T.; Kissner, T.L.; Ulrich, R.G. Synthetic Toll-like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome. Clin. Vaccine Immunol. 2007, 14, 1499–1504.
  91. Adanitsch, F.; Ittig, S.; Stöckl, J.; Oblak, A.; Haegman, M.; Jerala, R.; Beyaert, R.; Kosma, P.; Zamyatina, A. Development of aGlcN(1⇿1)aMan-based Lipid A mimetics as a novel class of potent Toll-like Receptor 4 agonists. J. Med. Chem. 2014, 57, 8056–8071.
  92. Adanitsch, F.; Shi, J.; Shao, F.; Beyaert, R.; Heine, H.; Zamyatina, A. Synthetic glycan-based TLR4 agonists targeting caspa-se-4/11 for the development of adjuvants and immunotherapeutics. Chem. Sci. 2018, 9, 3957–3963.
  93. Gordya, N.; Yakovlev, A.; Kruglikova, A.; Tulin, D.; Potolitsina, E.; Suborova, T.; Bordo, D.; Rosano, C.; Chernysh, S. Natural antimicrobial peptide complexes in the fighting of antibiotic resistant biofilms: Calliphora vicina medicinal maggots. PLoS ONE 2017, 12, e0173559.
  94. Chernysh, S.; Kozuharova, I. Anti-tumor activity of a peptide combining patterns of insect alloferons and mammalian immunoglobulins in naïve and tumor antigen vaccinated mice. Int. Immunopharmacol. 2013, 17, 1090–1093.
  95. Kim, Y.; Lee, S.K.; Bae, S.; Kim, H.; Park, Y.; Chu, N.K.; Kim, S.G.; Kim, H.-R.; Hwang, Y.-I.; Kang, J.S.; et al. The anti-inflammatory effect of alloferon on UVB-induced skin inflammation through the down-regulation of pro-inflammatory cytokines. Immunol. Lett. 2013, 149, 110–118.
  96. Griffin, M.E.; Hespen, C.W.; Wang, Y.; Hang, H.C. Translation of peptidoglycan metabolites into immunotherapeutics. Clin. Transl. Immunol. 2019, 8, e1095.
  97. Magalhaes, J.G.; Fritz, J.H.; Le Bourhis, L.; Sellge, G.; Travassos, L.H.; Selvanantham, T.; Girardin, S.E.; Gommerman, J.L.; Philpott, D.J. Nod2-Dependent Th2 Polarization of Antigen-Specific Immunity. J. Immunol. 2008, 181, 7925–7935.
  98. Rubino, S.J.; Magalhaes, J.G.; Philpott, D.; Bahr, G.M.; Blanot, D.; Girardin, S.E. Identification of a synthetic muramyl pep-tide derivative with enhanced Nod2 stimulatory capacity. Innate. Immun. 2013, 19, 493–503.
  99. Maisonneuve, C.; Bertholet, S.; Philpott, D.J.; De Gregorio, E. Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants. Proc. Natl. Acad. Sci. USA 2014, 111, 12294–12299.
  100. Bumgardner, S.A.; Zhang, L.; LaVoy, A.S.; Andre, B.; Frank, C.B.; Kajikawa, A.; Klaenhammer, T.R.; Dean, G.A. Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform. PLoS ONE 2018, 13, e0196950.
  101. Jackson, E.M.; Herbst-Kralovetz, M.M. Intranasal Vaccination with Murabutide Enhances Humoral and Mucosal Immune Responses to a Virus-Like Particle Vaccine. PLoS ONE 2012, 7, e41529.
  102. Nabergoj, S.; Mlinarič-Raščan, I.; Jakopin, Ž. Harnessing the untapped potential of nucleotide-binding oligomerization domain ligands for cancer immunotherapy. Med. Res. Rev. 2019, 39, 1447–1484.
  103. Jakopin, Z. Murabutide Revisited: A Review of its Pleiotropic Biological Effects. Curr. Med. Chem. 2013, 20, 2068–2079.
  104. Telzak, E.; Wolff, S.M.; Dinarello, C.A.; Conlon, T.; El Kholy, A.; Bahr, G.M.; Choay, J.P.; Morin, A.; Chedid, L. Clinical Evaluation of the Immunoadjuvant Murabutide, a Derivative of MDP, Administered with a Tetanus Toxoid Vaccine. J. Infect. Dis. 1986, 153, 628–633.
  105. Przewlocki, G.; Audibert, F.; Jolivet, M.; Chedid, L.; Kent, S.B.; Neurath, A.R. Production of antibodies recognizing a hepa-titis B virus (HBV) surface antigen by administration of murabutide associated to a synthetic pre-S HBV peptide conjugated to a toxoid carrier. Biochem. Biophys. Res. Commun. 1986, 140, 557–564.
  106. Byars, N.E.; Nakano, G.; Welch, M.; Lehman, D.; Allison, A.C. Improvement of hepatitis B vaccine by the use of a new adju-vant. Vaccine 1991, 9, 309–318.
  107. Keefer, M.C.; Graham, B.S.; McElrath, M.J.; Matthews, T.J.; Stablein, D.M.; Corey, L.; Wright, P.F.; Lawrence, D.; Fast, P.E.; Weinhold, K.; et al. Safety and immunogenicity of Env 2-3, a human immunode-ficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. AIDS Res. Hum. Retrov. 1996, 12, 683–693.
  108. Tamura, M.; Yoo, Y.C.; Yoshimatsu, K.; Yoshida, R.; Oka, T.; Ohkuma, K.; Arikawa, J.; Azuma, I. Effects of muramyl dipep-tide derivatives as adjuvants on the induction of antibody response to recombinant hepatitis B surface antigen. Vaccine 1995, 13, 77–82.
  109. Yoo, Y.C.; Yoshimatsu, K.; Koike, Y.; Hatsuse, R.; Yamanishi, K.; Tanishita, O.; Arikawa, J.; Azuma, I. Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine. Vaccine 1998, 16, 216–224.
  110. Effenberg, R.; Turánek Knötigová, P.; Zyka, D.; Célechovská, H.; Mašek, J.; Bartheldyová, E.; Hubatka, F.; Koudelka, S.; Lukáč, R.; Kovalová, A.; et al. Nonpyrogenic molecular adjuvants based on norAbu-muramyldipeptide and norAbu-glucosaminyl muramyldipeptide: Synthesis, molecular mechanisms of action, and biological activities in vitro and in vivo. J. Med. Chem. 2017, 60, 7745–7763.
  111. Yang, H.Z.; Xu, S.; Liao, X.Y.; Zhang, S.D.; Liang, Z.L.; Liu, B.H.; Bai, J.Y.; Jiang, C.; Ding, J.; Cheng, G.F.; et al. A Novel Immunostimulator, N2-[α-O-Benzyl-N-(acetylmuramyl)-l-alanyl-d- isoglutaminyl]-N6-trans-(m-nitrocinnamoyl)-l-lysine, and Its Adjuvancy on the Hepatitis B Surface Antigen. J. Med. Chem. 2005, 48, 5112–5122.
  112. Gobec, M.; Tomašič, T.; Štimac, A.; Frkanec, R.; Trontelj, J.; Anderluh, M.; Mlinarič-Raščan, I.; Jakopin, Ž. Discovery of na-nomolar desmuramylpeptide agonists of the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (NOD2) possessing immunostimulatory properties. J. Med. Chem. 2018, 61, 2707–2724.
  113. Fernández-Tejada, A.; Tan, D.S.; Gin, D.Y. Development of Improved Vaccine Adjuvants Based on the Saponin Natural Product QS-21 through Chemical Synthesis. Acc. Chem. Res. 2016, 49, 1741–1756.
  114. Pifferi, C.; Fuentes, R.; Fernández-Tejada, A. Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action. Nat. Rev. Chem. 2021, 5, 197–216.
  115. Fernández-Tejada, A. Design, synthesis and evaluation of optimized saponin variants derived from the vaccine adjuvant QS-21. Pure Appl. Chem. 2017, 89, 1359–1378.
  116. Fuentes, R.; Ruiz-de-Angulo, A.; Sacristán, N.; Navo, C.D.; Jiménez-Osés, G.; Anguita, J.; Fernández-Tejada, A. Replacing the Rhamnose-Xylose Moiety of QS-21 with Simpler Terminal Disaccharide Units Attenuates Adjuvant Activity in Truncated Saponin Variants. Chem. Eur. J. 2021, 27, 4731–4737.
  117. Fernández-Tejada, A.; Chea, E.K.; George, C.; Pillarsetty, N.V.K.; 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.
  118. Ghirardello, M.; Ruiz-de-Angulo, A.; Sacristan, N.; Barriales, D.; Jiménez-Barbero, J.; Poveda, A.; Corzana, F.; Anguita, J.; Fernández-Tejada, A. Exploting structure–activity relationships of QS-21 in the design and synthesis of streamlined saponin vaccine adjuvants. Chem. Commun. 2020, 56, 719–722.
  119. Le, T.T.; Cramer, J.P.; Chen, R.; Mayhew, S. Evolution of the COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 2020, 19, 667–668.
  120. Jeyanathan, M.; Afkhami, S.; Smaill, F.; Miller, M.S.; Lichty, B.D.; Xing, Z. Immunological considerations for COVID-19 vaccine strategies. Nat. Rev. Immunol. 2020, 20, 1–18.
  121. Huang, X.; Wang, X.; Zhang, J.; Xia, N.; Zhao, Q. Escherichia coli-derived virus-like particles in vaccine development. Npj Vaccines 2017, 2, 1–9.
  122. Donaldson, B.; Lateef, Z.; Walker, G.F.; Young, S.L.; Ward, V.K. Virus-like particle vaccines: Immunology and formula-tion for clinical translation. Expert. Rev. Vaccines 2018, 17, 833–849.
  123. Ward, B.J.; Gobeil, P.; Séguin, A.; Atkins, J.; Boulay, I.; Charbonneau, P.Y.; Couture, M.; D’Aoust, M.-A.; Dhaliwall, J.; Finkle, C.; et al. Phase 1 trial of a Candidate Recombinant Virus-Like Particle Vaccine for Covid-19 Disease Produced in Plants. medRxiv 2020.
  124. Gursel, M.; Gursel, I. Development of CpG ODN Based Vaccine Adjuvant Formulations. Adv. Struct. Saf. Stud. 2016, 1404, 289–298.
  125. Bode, C.; Zhao, G.; Steinhagen, F.; Kinjo, T.; Klinman, D.M. CpG DNA as a vaccine adjuvant. Expert Rev. Vaccines 2011, 10, 499–511.
  126. Klimek, L.; Willers, J.; Hammann-Haenni, A.; Pfaar, O.; Stocker, H.; Mueller, P.; Renner, W.A.; Bachmann, M.F. Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: A phase IIb study. Clin. Exp. Allergy 2011, 41, 1305–1312.
More
Video Production Service