Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Immunological Mechanism and Clinical Application of PAMP Adjuvants

Author(s): Yu Yan, Dan Yao and Xiaoyu Li*

Volume 16, Issue 1, 2021

Published on: 01 February, 2021

Page: [30 - 43] Pages: 14

DOI: 10.2174/1574892816666210201114712

Price: $65


Background: The host innate immune system can recognize Pathogen-Associated Molecular Patterns (PAMPs) through Pattern Recognition Receptors (PRRs), thereby initiating innate immune responses and subsequent adaptive immune responses. PAMPs can be developed as a vaccine adjuvant for modulating and optimizing antigen-specific immune responses, especially in combating viral infections and tumor therapy. Although several PAMP adjuvants have been successfully developed they are still lacking in general, and many of them are in the preclinical exploration stage.

Objective: This review summarizes the research progress and development direction of PAMP adjuvants, focusing on their immune mechanisms and clinical applications.

Methods: PubMed, Scopus, and Google Scholar were screened for this information. We highlight the immune mechanisms and clinical applications of PAMP adjuvants.

Results: Because of the differences in receptor positions, specific immune cells targets, and signaling pathways, the detailed molecular mechanism and pharmacokinetic properties of one agonist cannot be fully generalized to another agonist, and each PAMP should be studied separately. In addition, combination therapy and effective integration of different adjuvants can increase the additional efficacy of innate and adaptive immune responses.

Conclusion: The mechanisms by which PAMPs exert adjuvant functions are diverse. With continuous discovery in the future, constant adjustments should be made to build new understandings. At present, the goal of therapeutic vaccination is to induce T cells that can specifically recognize and eliminate tumor cells and establish long-term immune memory. Following immune checkpoint modulation therapy, cancer treatment vaccines may be an option worthy of clinical testing.

Keywords: Adjuvant, clinical application, immunological mechanism, immune responses, PAMP, pattern recognition receptors.

Powell BS, Andrianov AK, Fusco PC. Polyionic vaccine adjuvants: Another look at aluminum salts and polyelectrolytes. Clin Exp Vaccine Res 2015; 4(1): 23-45.
[] [PMID: 25648619]
Dalpke A, Zimmermann S, Heeg K. Immunopharmacology of CpG DNA. Biol Chem 2002; 383(10): 1491-500.
[] [PMID: 12452427]
Bauer S, Kirschning CJ, Häcker H, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA 2001; 98(16): 9237-42.
[] [PMID: 11470918]
Yin X, Langer S, Zhang Z, et al. Sensor sensibility-HIV-1 and the innate immune response. Cells 2020; 9(1): 254.
[] [PMID: 31968566]
Miyaji EN, Carvalho E, Oliveira ML, Raw I, Ho PL. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants. Braz J Med Biol Res 2011; 44(6): 500-13.
[] [PMID: 21584443]
Mills KHG. TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol 2011; 11(12): 807-22.
[] [PMID: 22094985]
Brisse M, Ly H. Comparative structure and function analysis of the RIG-I-like receptors: RIG-I and MDA5. Front Immunol 2019; 10: 1586.
[] [PMID: 31379819]
Chow KT, Gale M Jr, Loo YM. RIG-I and other RNA sensors in antiviral immunity. Annu Rev Immunol 2018; 36: 667-94.
[] [PMID: 29677479]
Kato H, Takeuchi O, Sato S, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441(7089): 101-5.
[] [PMID: 16625202]
Kato H, Sato S, Yoneyama M, et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity 2005; 23(1): 19-28.
[] [PMID: 16039576]
Errett JS, Suthar MS, McMillan A, Diamond MS, Gale M Jr. The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection. J Virol 2013; 87(21): 11416-25.
[] [PMID: 23966395]
Kasumba DM, Grandvaux N. Therapeutic targeting of RIG-I and MDA5 might not lead to the same Rome. Trends Pharmacol Sci 2019; 40(2): 116-27.
[] [PMID: 30606502]
Salem ML, El-Naggar SA, Kadima A, Gillanders WE, Cole DJ. The adjuvant effects of the toll-like receptor 3 ligand polyinosinic- cytidylic acid poly (I:C) on antigen-specific CD8+ T cell responses are partially dependent on NK cells with the induction of a beneficial cytokine milieu. Vaccine 2006; 24(24): 5119-32.
[] [PMID: 16704888]
Trumpfheller C, Caskey M, Nchinda G, et al. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA 2008; 105(7): 2574-9.
[] [PMID: 18256187]
Martins KA, Bavari S, Salazar AM. Vaccine adjuvant uses of poly-IC and derivatives. Expert Rev Vaccines 2015; 14(3): 447-59.
[] [PMID: 25308798]
Linehan MM, Dickey TH, Molinari ES, et al. A minimal RNA ligand for potent RIG-I activation in living mice. Sci Adv 2018; 4(2): e1701854.
[] [PMID: 29492454]
Alvarez FJ. The effect of chitin size, shape, source and purification method on immune recognition. Molecules 2014; 19(4): 4433-51.
[] [PMID: 24727416]
Zhang M, Kim JA, Huang AY. Optimizing tumor microenvironment for cancer immunotherapy: β-glucan-based nanoparticles. Front Immunol 2018; 9: 341.
[] [PMID: 29535722]
Hou B, Reizis B, DeFranco AL. Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms. Immunity 2008; 29(2): 272-82.
[] [PMID: 18656388]
Jin JW, Tang SQ, Rong MZ, Zhang MQ. Synergistic effect of dual targeting vaccine adjuvant with aminated β-glucan and CpG-oligodeoxynucleotides for both humoral and cellular immune responses. Acta Biomater 2018; 78: 211-23.
[] [PMID: 30098441]
Elieh Ali Komi D, Sharma L, Dela Cruz CS. Chitin and its effects on inflammatory and immune responses. Clin Rev Allergy Immunol 2018; 54(2): 213-23.
[] [PMID: 28251581]
Leleux JA, Pradhan P, Roy K. Biophysical attributes of CpG presentation control TLR9 signaling to differentially polarize systemic immune responses. Cell Rep 2017; 18(3): 700-10.
[] [PMID: 28099848]
Lee J, Park EB, Min J, et al. Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies. Nucleic Acids Res 2018; 46(19): 10533.
[] [PMID: 30202915]
Campbell JD. Development of the CpG Adjuvant 1018: A case study. Methods Mol Biol 2017; 1494: 15-27.
[] [PMID: 27718183]
Zhao X, Zhang Z, Moreira D, et al. B cell lymphoma immunotherapy using TLR9-targeted oligonucleotide STAT3 inhibitors. Mol Ther 2018; 26(3): 695-707.
[] [PMID: 29433938]
Reed KA, Hobert ME, Kolenda CE, et al. The Salmonella typhimurium flagellar basal body protein FliE is required for flagellin production and to induce a proinflammatory response in epithelial cells. J Biol Chem 2002; 277(15): 13346-53.
[] [PMID: 11821427]
Cui B, Liu X, Fang Y, Zhou P, Zhang Y, Wang Y. Flagellin as a vaccine adjuvant. Expert Rev Vaccines 2018; 17(4): 335-49.
[] [PMID: 29580106]
Joffre O, Nolte MA, Spörri R, Reis e Sousa C. Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol Rev 2009; 227(1): 234-47.
[] [PMID: 19120488]
Gutjahr A, Papagno L, Nicoli F, et al. Cutting edge: A dual TLR2 and TLR7 ligand induces highly potent humoral and cell-mediated immune responses. J Immunol 2017; 198(11): 4205-9.
[] [PMID: 28432147]
Ding J, Ning Y, Bai Y, Xu X, Sun X, Qi C. β-Glucan induces autophagy in dendritic cells and influences T-cell differentiation. Med Microbiol Immunol (Berl) 2019; 208(1): 39-48.
[] [PMID: 30088084]
Desch AN, Gibbings SL, Clambey ET, et al. Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction. Nat Commun 2014; 5: 4674.
[] [PMID: 25135627]
Welsh RM, Waggoner SN. NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology 2013; 435(1): 37-45.
[] [PMID: 23217614]
Oth T, Van Elssen CHMJ, Schnijderberg MCA, et al. Potency of both human Th1 and NK helper cell activation is determined by IL-12p70-producing PAMP-matured DCs. J Interferon Cytokine Res 2015; 35(9): 748-58.
[] [PMID: 26134473]
Demaria O, Cornen S, Daëron M, Morel Y, Medzhitov R, Vivier E. Harnessing innate immunity in cancer therapy. Nature 2019; 574(7776): 45-56.
[] [PMID: 31578484]
Su F, Song Q, Zhang C, et al. A β-1,3/1,6-glucan from Durvillaea antarctica inhibits tumor progression in vivo as an immune stimulator. Carbohydr Polym 2019; 222: 114993.
[] [PMID: 31320068]
Shi SH, Yang WT, Huang KY, et al. β-glucans from Coriolus versicolor protect mice against S. typhimurium challenge by activation of macrophages. Int J Biol Macromol 2016; 86: 352-61.
[] [PMID: 26802244]
Alexander MP, Fiering SN, Ostroff GR, Cramer RA, Mullins DW. Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung. Cancer Immunol Immunother 2018; 67(11): 1731-42.
[] [PMID: 30167860]
Liu J, Gunn L, Hansen R, Yan J. Combined yeast-derived β-glucan with anti-tumor monoclonal antibody for cancer immunotherapy. Exp Mol Pathol 2009; 86(3): 208-14.
[] [PMID: 19454271]
Hong F, Hansen RD, Yan J, et al. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res 2003; 63(24): 9023-31.
[PMID: 14695221]
Bose N. Beta-glucan immunotherapies affecting the immune microenvironment. MN20190022129, 2019.
Bose N. Beta-glucan in combination with anti- cancer agents affecting the tumor microenvironment. MN20190060351, 2019.
Wilbers RHP, Westerhof LB, van de Velde J, et al. Physical interaction of T cells with dendritic cells is not required for the immunomodulatory effects of the edible mushroom Agaricus subrufescens. Front Immunol 2016; 7: 519.
[] [PMID: 27920777]
Dalpke AH, Heeg K. CpG-DNA as immune response modifier. Int J Med Microbiol 2004; 294(5): 345-54.
[] [PMID: 15532993]
Bracho G, Lastre M, del Campo J, et al. Proteoliposome derived cochleate as novel adjuvant. Vaccine 2006; 24(Suppl. 2): S2-301.
[] [PMID: 16823914]
Flores-Langarica A, Bobat S, Marshall JL, et al. Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production. Eur J Immunol 2015; 45(8): 2299-311.
[] [PMID: 26036767]
Van Dyken SJ, Mohapatra A, Nussbaum JC, et al. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and γδ T cells. Immunity 2014; 40(3): 414-24.
[] [PMID: 24631157]
Rop O, Mlcek J, Jurikova T. Beta-glucans in higher fungi and their health effects. Nutr Rev 2009; 67(11): 624-31.
[] [PMID: 19906249]
Hayashi T, Momota M, Kuroda E, et al. DAMP-inducing adjuvant and PAMP adjuvants parallelly enhance protective type-2 and type-1 immune responses to influenza split vaccination. Front Immunol 2018; 9: 2619.
[] [PMID: 30515151]
Mount A, Koernig S, Silva A, Drane D, Maraskovsky E, Morelli AB. Combination of adjuvants: The future of vaccine design. Expert Rev Vaccines 2013; 12(7): 733-46.
[] [PMID: 23885819]
Halliday A, Turner JD, Guimarães A, Bates PA, Taylor MJ. The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models. Parasit Vectors 2016; 9(1): 96.
[] [PMID: 26897363]
Redecke V, Häcker H, Datta SK, et al. Cutting edge: Activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 2004; 172(5): 2739-43.
[] [PMID: 14978071]
Kennedy R, Celis E. Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol Rev 2008; 222: 129-44.
[] [PMID: 18363998]
Germann T, Bongartz M, Dlugonska H, et al. Interleukin-12 profoundly up-regulates the synthesis of antigen-specific complement-fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo. Eur J Immunol 1995; 25(3): 823-9.
[] [PMID: 7705414]
Allen AC, Wilk MM, Misiak A, Borkner L, Murphy D, Mills KHG. Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells. Mucosal Immunol 2018; 11(6): 1763-76.
[] [PMID: 30127384]
Bär E, Gladiator A, Bastidas S, et al. A novel Th cell epitope of Candida albicans mediates protection from fungal infection. J Immunol 2012; 188(11): 5636-43.
[] [PMID: 22529294]
Zimmermann S, Egeter O, Hausmann S, et al. CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J Immunol 1998; 160(8): 3627-30.
[PMID: 9558060]
Sparwasser T, Vabulas RM, Villmow B, Lipford GB, Wagner H. Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins. Eur J Immunol 2000; 30(12): 3591-7.
[<3591::AID-IMMU3591>3.0.CO;2-J] [PMID: 11169401]
Chiodetti AL, Sánchez Vallecillo MF, Dolina JS, et al. Class-B CpG-ODN Formulated with a nanostructure induces type I interferons-dependent and CD4+ T cell-independent CD8+ T-Cell response against unconjugated protein antigen. Front Immunol 2018; 9: 2319.
[] [PMID: 30364187]
Johnson S, Zhan Y, Sutherland RM, et al. Selected Toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells. Immunity 2009; 30(2): 218-27.
[] [PMID: 19200758]
Le Bon A, Etchart N, Rossmann C, et al. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol 2003; 4(10): 1009-15.
[] [PMID: 14502286]
Dunn GP, Bruce AT, Sheehan KCF, et al. A critical function for type I interferons in cancer immunoediting. Nat Immunol 2005; 6(7): 722-9.
[] [PMID: 15951814]
Diamond MS, Kinder M, Matsushita H, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 2011; 208(10): 1989-2003.
[] [PMID: 21930769]
Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med 2000; 192(5): 755-60.
[] [PMID: 10974040]
Bose A, Chakraborty K, Sarkar K, et al. Neem leaf glycoprotein induces perforin-mediated tumor cell killing by T and NK cells through differential regulation of IFNgamma signaling. J Immunother 2009; 32(1): 42-53.
[] [PMID: 19307993]
Schmaltz C, Alpdogan O, Kappel BJ, et al. T cells require TRAIL for optimal graft-versus-tumor activity. Nat Med 2002; 8(12): 1433-7.
[] [PMID: 12426560]
Norian LA, Kresowik TP, Rosevear HM, et al. Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-Related Apoptosis-Inducing Ligand (TRAIL)/CpG immunotherapy. PLoS One 2012; 7(2): e31085.
[] [PMID: 22312440]
VanOosten RL, Griffith TS. Activation of tumor-specific CD8+ T Cells after intratumoral Ad5-TRAIL/CpG oligodeoxynucleotide combination therapy. Cancer Res 2007; 67(24): 11980-90.
[] [PMID: 18089829]
Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: Implications for vaccine design. Nat Rev Immunol 2008; 8(4): 247-58.
[] [PMID: 18323851]
Todryk SM. T Cell memory to vaccination. Vaccines (Basel) 2018; 6(4): 84.
[] [PMID: 30558246]
Youngblood B, Hale JS, Kissick HT, et al. Effector CD8 T cells dedifferentiate into long-lived memory cells. Nature 2017; 552(7685): 404-9.
[] [PMID: 29236683]
Marino J, Gonzalez-Nolasco B, Wang X, Orent W, Benichou G. Contrasting effects of B cell depletion on CD4+ and CD8+ memory T cell responses generated after transplantation. Am J Transplant 2020; 20(9): 2551-8.
[] [PMID: 32185859]
Siefert AL, Caplan MJ, Fahmy TM. Artificial bacterial biomimetic nanoparticles synergize pathogen-associated molecular patterns for vaccine efficacy. Biomaterials 2016; 97: 85-96.
[] [PMID: 27162077]
de Titta A, Ballester M, Julier Z, et al. Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose. Proc Natl Acad Sci USA 2013; 110(49): 19902-7.
[] [PMID: 24248387]
Dai H, Lan P, Zhao D, et al. PIRs mediate innate myeloid cell memory to nonself MHC molecules. Science 2020; 368(6495): 1122-7.
[] [PMID: 32381589]
Unutmaz D, Pileri P, Abrignani S. Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J Exp Med 1994; 180(3): 1159-64.
[] [PMID: 8064232]
Davila E, Velez MG, Heppelmann CJ, Celis E. Creating space: An antigen-independent, CpG-induced peripheral expansion of naive and memory T lymphocytes in a full T-cell compartment. Blood 2002; 100(7): 2537-45.
[] [PMID: 12239167]
Oh JZ, Ravindran R, Chassaing B, et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 2014; 41(3): 478-92.
[] [PMID: 25220212]
Tian J, Ma J, Ma K, et al. β-Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid-derived suppressor cells. Eur J Immunol 2013; 43(5): 1220-30.
[] [PMID: 23424024]
Albeituni SH, Ding C, Liu M, et al. Yeast-derived particulate β-glucan treatment subverts the suppression of Myeloid-Derived Suppressor Cells (MDSC) by inducing polymorphonuclear MDSC apoptosis and monocytic MDSC differentiation to APC in cancer. J Immunol 2016; 196(5): 2167-80.
[] [PMID: 26810222]
Osorio F, LeibundGut-Landmann S, Lochner M, et al. DC activated via dectin-1 convert Treg into IL-17 producers. Eur J Immunol 2008; 38(12): 3274-81.
[] [PMID: 19039774]
Li J, O’Malley M, Urban J, et al. Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer. Mol Ther 2011; 19(4): 650-7.
[] [PMID: 21266959]
Huleatt JW, Jacobs AR, Tang J, et al. Vaccination with recombinant fusion proteins incorporating Toll-like receptor ligands induces rapid cellular and humoral immunity. Vaccine 2007; 25(4): 763-75.
[] [PMID: 16968658]
Wille-Reece U, Flynn BJ, Loré K, et al. HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci USA 2005; 102(42): 15190-4.
[] [PMID: 16219698]
Wille-Reece U, Wu CY, Flynn BJ, Kedl RM, Seder RA. Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses. J Immunol 2005; 174(12): 7676-83.
[] [PMID: 15944268]
Oh JZ, Kedl RM. The capacity to induce cross-presentation dictates the success of a TLR7 agonist-conjugate vaccine for eliciting cellular immunity. J Immunol 2010; 185(8): 4602-8.
[] [PMID: 20844205]
Cho HI, Jung SH, Sohn HJ, Celis E, Kim TG. An optimized peptide vaccine strategy capable of inducing multivalent CD8+ T cell responses with potent antitumor effects. OncoImmunology 2015; 4(11): e1043504.
[] [PMID: 26451316]
Ahonen CL, Doxsee CL, McGurran SM, et al. Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med 2004; 199(6): 775-84.
[] [PMID: 15007094]
Kobiyama K, Temizoz B, Kanuma T, et al. Species-dependent role of type I IFNs and IL-12 in the CTL response induced by humanized CpG complexed with β-glucan. Eur J Immunol 2016; 46(5): 1142-51.
[] [PMID: 26786557]
Mochizuki S, Morishita H, Kobiyama K, Aoshi T, Ishii KJ, Sakurai K. Immunization with antigenic peptides complexed with beta-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs. J Control Release 2015; 220(Pt A): 495-502.
Miyamoto N, Mochizuki S, Sakurai K. Designing an immunocyte- targeting delivery system by use of beta-glucan. Vaccine 2018; 36(1): 186-9.
[] [PMID: 29174675]
Derouazi M. Combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for use in medicine. CH20190175748, 2019.
Ballester M, Jeanbart L, de Titta A, et al. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice. Sci Rep 2015; 5: 14274.
[] [PMID: 26387548]
Leleux J, Roy K. Micro and nanoparticle-based delivery systems for vaccine immunotherapy: An immunological and materials perspective. Adv Healthc Mater 2013; 2(1): 72-94.
[] [PMID: 23225517]
Kuroda E, Coban C, Ishii KJ. Particulate adjuvant and innate immunity: Past achievements, present findings, and future prospects. Int Rev Immunol 2013; 32(2): 209-20.
[] [PMID: 23570316]
Moyer TJ, Zmolek AC, Irvine DJ. Beyond antigens and adjuvants: Formulating future vaccines. J Clin Invest 2016; 126(3): 799-808.
[] [PMID: 26928033]
Wang X, Li X, Ito A, Sogo Y, Ohno T. Pore size-dependent immunogenic activity of mesoporous silica-based adjuvants in cancer immunotherapy. J Biomed Mater Res A 2014; 102(4): 967-74.
[] [PMID: 23650285]
Chan ASH, Jonas AB, Qiu X, et al. Imprime PGG-mediated anti-cancer immune activation requires immune complex formation. PLoS One 2016; 11(11): e0165909.
[] [PMID: 27812183]
Stier H, Ebbeskotte V, Gruenwald J. Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan. Nutr J 2014; 13: 38.
[] [PMID: 24774968]
Sandvik A, Wang YY, Morton HC, Aasen AO, Wang JE, Johansen FE. Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats. Clin Exp Immunol 2007; 148(1): 168-77.
[] [PMID: 17349015]
Soria I, Myhre P, Horton V, et al. Effect of food on the pharmacokinetics and bioavailability of oral imiquimod relative to a subcutaneous dose. Int J Clin Pharmacol Ther 2000; 38(10): 476-81.
[] [PMID: 11073288]
Fehres CM, Bruijns SCM, van Beelen AJ, et al. Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T-cell cross-priming. Eur J Immunol 2014; 44(8): 2415-24.
[] [PMID: 24825342]
Oth T, Vanderlocht J, Van Elssen CH, Bos GM, Germeraad WT. Pathogen-associated molecular patterns induced crosstalk between dendritic cells, T helper cells, and natural killer helper cells can improve dendritic cell vaccination. Mediators Inflamm 2016; 2016
[] [PMID: 26980946]
Shimizu K, Fujii S. An adjuvant role of in situ Dendritic Cells (DCs) in linking innate and adaptive immunity. Front Biosci 2008; 13: 6193-201.
[] [PMID: 18508653]
O’Hagan DT, MacKichan ML, Singh M. Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 2001; 18(3): 69-85.
[] [PMID: 11566599]
Gouttefangeas C, Rammensee HG. Personalized cancer vaccines: Adjuvants are important, too. Cancer Immunol Immunother 2018; 67(12): 1911-8.
[] [PMID: 29644387]
Hafner AM, Corthésy B, Merkle HP. Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant. Adv Drug Deliv Rev 2013; 65(10): 1386-99.
[] [PMID: 23751781]
Wu TYH. Strategies for designing synthetic immune agonists. Immunology 2016; 148(4): 315-25.
[] [PMID: 27213842]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy