Advances in the design and delivery of peptide subunit vaccines with a focus on Toll-like receptor agonists

References

• Babiuk LA. Broadening the approaches to developing more effective vaccines. Vaccine17(13–14), 1587–1595 (1999).
   PubMed Web of Science ®Google Scholar
• Brown F. Peptide vaccines: fantasy or reality? World J. Microbiol. Biotechnol.8(Suppl. 1), 52–53 (1992).
   PubMed Web of Science ®Google Scholar
• Levine MM, Sztein MB. Vaccine development strategies for improving immunization: the role of modern immunology. Nat. Immunol.5(5), 460–464 (2004).
   PubMed Web of Science ®Google Scholar
• O’Hagan DT, De Gregorio E. The path to a successful vaccine adjuvant – ‘the long and winding road’. Drug Discov. Today14(11–12), 541–551 (2009).
   PubMed Web of Science ®Google Scholar
• Purcell AW, Zeng W, Mifsud NA, Ely LK, Macdonald WA, Jackson DC. Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design. J. Pept. Sci.9(5), 255–281 (2003).
   PubMedGoogle Scholar
• Vos Q, Lees A, Wu ZQ, Snapper CM, Mond JJ. B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms. Immunol. Rev.176, 154–170 (2000).
   PubMed Web of Science ®Google Scholar
• Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu. Rev. Immunol.13, 655–692 (1995).
   PubMed Web of Science ®Google Scholar
• Bachmann MF, Zinkernagel RM. Neutralizing antiviral B cell responses. Annu. Rev. Immunol.15, 235–270 (1997).
   PubMed Web of Science ®Google Scholar
• Dintzis HM, Dintzis RZ, Vogelstein B. Molecular determinants of immunogenicity: the immunon model of immune response. Proc. Natl Acad. Sci. USA73(10), 3671–3675 (1976).
   PubMed Web of Science ®Google Scholar
• Sulzer B, Perelson AS. Immunons revisited: binding of multivalent antigens to B cells. Mol. Immunol.34(1), 63–74 (1997).
   PubMedGoogle Scholar
• Tam JP. Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl Acad. Sci. USA85(15), 5409–5413 (1988).
   PubMed Web of Science ®Google Scholar
• Tam JP, Clavijo P, Lu YA, Nussenzweig V, Nussenzweig R, Zavala F. Incorporation of T and B epitopes of the circumsporozoite protein in a chemically defined synthetic vaccine against malaria. J. Exp. Med.171(1), 299–306 (1990).
   PubMed Web of Science ®Google Scholar
• Sakarellos-Daitsiotis M, Krikorian D, Panou-Pomonis E, Sakarellos C. Artificial carriers: a strategy for constructing antigenic/immunogenic conjugates. Curr. Top. Med. Chem.6(16), 1715–1735 (2006).
   PubMedGoogle Scholar
• Niederhafner P, Reinis M, Sebestik J, Jezek J. Glycopeptide dendrimers, part III: a review. Use of glycopeptide dendrimers in immunotherapy and diagnosis of cancer and viral diseases. J. Pept. Sci.14(5), 556–587 (2008).
   PubMedGoogle Scholar
• Reimer U. Prediction of linear B-cell epitopes. Methods Mol. Biol.524, 335–344 (2009).
   PubMedGoogle Scholar
• Greenbaum JA, Andersen PH, Blythe M et al. Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools. J. Mol. Recognit.20(2), 75–82 (2007).
   PubMed Web of Science ®Google Scholar
• Relf WA, Cooper J, Brandt ER et al. Mapping a conserved conformational epitope from the M protein of group A streptococci. Pept. Res.9(1), 12–20 (1996).
   PubMedGoogle Scholar
• Hayman WA, Brandt ER, Relf WA, Cooper J, Saul A, Good MF. Mapping the minimal murine T cell and B cell epitopes within a peptide vaccine candidate from the conserved region of the M protein of group A streptococcus. Int. Immunol.9(11), 1723–1733 (1997).
   PubMed Web of Science ®Google Scholar
• Gore T, Dori Y, Talmon Y, Tirrell M, Bianco-Peled H. Self-assembly of model collagen peptide amphiphiles. Langmuir17(17), 5352–5360 (2001).
   Web of Science ®Google Scholar
• Yu YC, Tirrell M, Fields GB. Minimal lipidation stabilizes protein-like molecular architecture. J. Am. Chem. Soc.120(39), 9979–9987 (1998).
   Web of Science ®Google Scholar
• Tu RS, Marullo R, Pynn R, Bitton R, Bianco-Peled H, Tirrell MV. Cooperative DNA binding and assembly by a bZip-peptide-amphiphile. Soft Matter DOI: 10.1039/b922295b (2009) (In press).
   Google Scholar
• Tong JC, Tan TW, Ranganathan S. Methods and protocols for prediction of immunogenic epitopes. Brief Bioinform.8(2), 96–108 (2007).
   PubMedGoogle Scholar
• van der Burg SH, Bijker MS, Welters MJP, Offringa R, Melief CJM. Improved peptide vaccine strategies, creating synthetic artificial infections to maximize immune efficacy. Adv. Drug Deliv. Rev.58(8), 916–930 (2006).
   PubMed Web of Science ®Google Scholar
• Bijker MS, van den Eeden SJF, Franken KL, Melief CJM, Offringa R, van der Burg SH. CD8+ CTL priming by exact peptide epitopes in incomplete Freund’s adjuvant induces a vanishing CTL response, whereas long peptides induce sustained CTL reactivity. J. Immunol.179(8), 5033–5040 (2007).
   PubMed Web of Science ®Google Scholar
• Le Gall S, Stamegna P, Walker BD. Portable flanking sequences modulate CTL epitope processing. J. Clin. Invest.117(11), 3563–3575 (2007).
   PubMed Web of Science ®Google Scholar
• Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol.9, 8 (2008).
   PubMed Web of Science ®Google Scholar
• Lin HH, Zhang GL, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research. BMC Bioinformatics9(Suppl. 12), S22 (2008).
   PubMed Web of Science ®Google Scholar
• Yu X, Owens GP, Gilden DH. Rapid and efficient identification of epitopes/mimotopes from random peptide libraries. J. Immunol. Methods316(1–2), 67–74 (2006).
   PubMedGoogle Scholar
• Stone JD, Demkowicz WE, Stern LJ. HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays. Proc. Natl Acad. Sci. USA102(10), 3744–3749 (2005).
   PubMedGoogle Scholar
• Helling F, Shang A, Calves M et al. GD3 vaccines for melanoma: superior immunogenicity of keyhole limpet hemocyanin conjugate vaccines. Cancer Res.54(1), 197–203 (1994).
   PubMed Web of Science ®Google Scholar
• Harris JR, Markl J. Keyhole limpet hemocyanin (KLH): a biomedical review. Micron30(6), 597–623 (1999).
   PubMed Web of Science ®Google Scholar
• Xu Q-H, Zhao X-N, Cheng J-P, Wei C-H, Zhang Q-H, Rong K-T. Influence of carrier proteins on the immunologic response to haptenic antitetrodotoxin vaccine. Bioconjug. Chem.17(6), 1508–1513 (2006).
   PubMedGoogle Scholar
• Herzenberg LA, Tokuhisa T. Carrier-priming leads to hapten-specific suppression. Nature285(5767), 664–667 (1980).
   PubMed Web of Science ®Google Scholar
• Schutze MP, Leclerc C, Jolivet M, Audibert F, Chedid L. Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J. Immunol.135(4), 2319–2322 (1985).
   PubMed Web of Science ®Google Scholar
• Kumar A, Arora R, Kaur P, Chauhan VS, Sharma P. ‘Universal’ T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide. J. Immunol.148(5), 1499–1505 (1992).
   PubMed Web of Science ®Google Scholar
• Zeng W, Ghosh S, Macris M, Pagnon J, Jackson DC. Assembly of synthetic peptide vaccines by chemoselective ligation of epitopes: influence of different chemical linkages and epitope orientations on biological activity. Vaccine19(28–29), 3843–3852 (2001).
   PubMedGoogle Scholar
• Finstad CL, Wang CY, Kowalski J et al. Synthetic luteinizing hormone releasing hormone (LHRH) vaccine for effective androgen deprivation and its application to prostate cancer immunotherapy. Vaccine22(9–10), 1300–1313 (2004).
   PubMedGoogle Scholar
• Singh M, O’Hagan D. Advances in vaccine adjuvants. Nat. Biotechnol.17(11), 1075–1081 (1999).
   PubMed Web of Science ®Google Scholar
• Reddy ST, Swartz MA, Hubbell JA. Targeting dendritic cells with biomaterials: developing the next generation of vaccines. Trends Immunol.27(12), 573–579 (2006).
   PubMed Web of Science ®Google Scholar
• Gupta RK, Siber GR. Adjuvants for human vaccines – current status, problems and future prospects. Vaccine13(14), 1263–1276 (1995).
   PubMed Web of Science ®Google Scholar
• Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol.5(10), 987–995 (2004).
   PubMed Web of Science ®Google Scholar
• Pulendran B. Modulating vaccine responses with dendritic cells and Toll-like receptors. Immunol. Rev.199(1), 227–250 (2004).
   PubMed Web of Science ®Google Scholar
• Wilson NS, El-Sukkari D, Belz GT et al. Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood102(6), 2187–2194 (2003).
   PubMed Web of Science ®Google Scholar
• Granucci F, Zanoni I, Ricciardi-Castagnoli P. Central role of dendritic cells in the regulation and deregulation of immune responses. Cell. Mol. Life Sci.65(11), 1683–1697 (2008).
   PubMedGoogle Scholar
• Spellberg B, Edwards John E. Type 1/type 2 immunity in infectious diseases. Clin. Infect. Dis.32(1), 76–102 (2001).
   PubMed Web of Science ®Google Scholar
• Gafa V, Lande R, Gagliardi MC et al. Human dendritic cells following Aspergillus fumigatus infection express the CCR7 receptor and a differential pattern of interleukin-12 (IL-12), IL-23, and IL-27 cytokines, which lead to a Th1 response. Infect. Immun.74(3), 1480–1489 (2006).
   PubMed Web of Science ®Google Scholar
• Macatonia SE, Hsieh CS, Murphy KM, Ogarra A. Dendritic cells and macrophages are required for Th1 development of CD4+ T-cells from α-β-TCR transgenic mice – IL-12 substitutions for macrophages to stimulate IFN-γ production is IFN-γ dependent. Int. Immunol.5(9), 1119–1128 (1993).
   PubMed Web of Science ®Google Scholar
• Laouini D, Alenius H, Bryce P, Oettgen H, Tsitsikov E, Geha RS. IL-10 is critical for Th2 responses in a murine model of allergic dermatitis. J. Clin. Invest.112(7), 1058–1066 (2003).
   PubMedGoogle Scholar
• Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J. Immunol.180(9), 5771–5777 (2008).
   PubMed Web of Science ®Google Scholar
• Perrie Y, Mohammed AR, Kirby DJ, McNeil SE, Bramwell VW. Vaccine adjuvant systems: enhancing the efficacy of sub-unit protein antigens. Int. J. Pharm.364(2), 272–280 (2008).
   PubMed Web of Science ®Google Scholar
• Kool M, Soullie T, van Nimwegen M et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J. Exp. Med.205(4), 869–882 (2008).
   PubMed Web of Science ®Google Scholar
• Kool M, Petrilli V, De Smedt T et al. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J. Immunol.181(6), 3755–3759 (2008).
   PubMed Web of Science ®Google Scholar
• Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat. Rev. Immunol.9(4), 287–293 (2009).
   PubMed Web of Science ®Google Scholar
• Bergfors E, Bjorkelund C, Trollfors B. Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines. Eur. J. Pediatr.164(11), 691–697 (2005).
   PubMed Web of Science ®Google Scholar
• Moylett EH, Hanson IC. Mechanistic actions of the risks and adverse events associated with vaccine administration. J. Allergy Clin. Immunol.114(5), 1010–1020 (2004).
   PubMedGoogle Scholar
• Ludewig B, Barchiesi F, Pericin M, Zinkernagel RM, Hengartner H, Schwendener RA. In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity. Vaccine19(1), 23–32 (2000).
   PubMed Web of Science ®Google Scholar
• Aucouturier J, Dupuis L, Deville S, Ascarateil S, Ganne V. Montanide ISA 720 and 51: a new generation of water in oil emulsions as adjuvants for human vaccines. Expert Rev. Vaccines1, 111–118 (2002).
   PubMed Web of Science ®Google Scholar
• Kenter GG, Welters MJP, Valentijn ARPM et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N. Engl. J. Med.361(19), 1838–1847 (2009).
   PubMed Web of Science ®Google Scholar
• Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity. Immunol. Rev.227, 221–233 (2009).
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. TLR signaling. Cell Death Differ.13(5), 816–825 (2006).
   PubMed Web of Science ®Google Scholar
• van Duin D, Medzhitov R, Shaw AC. Triggering TLR signaling in vaccination. Trends Immunol.27(1), 49–55 (2006).
   PubMed Web of Science ®Google Scholar
• Skokos D, Nussenzweig MC. CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J. Exp. Med.204(7), 1525–1531 (2007).
   PubMed Web of Science ®Google Scholar
• Redecke V, Hacker H, Datta SK et al. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J. Immunol.172(5), 2739–2743 (2004).
   PubMed Web of Science ®Google Scholar
• Yang D, Chen Q, Su SB et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2 MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J. Exp. Med.205(1), 79–90 (2008).
   PubMed Web of Science ®Google Scholar
• Malherbe L, Mark L, Fazilleau N, McHeyzer-Williams LJ, McHeyzer-Williams MG. Vaccine adjuvants alter TCR-based selection thresholds. Immunity28(5), 698–709 (2008).
   PubMed Web of Science ®Google Scholar
• Wille-Reece U, Flynn BJ, Lore K et al. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J. Exp. Med.203(5), 1249–1258 (2006).
   PubMed Web of Science ®Google Scholar
• Dupont J, Altclas J, Lepetic A et al. A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine. Vaccine24(49–50), 7167–7174 (2006).
   PubMed Web of Science ®Google Scholar
• Ellis RD, Mullen GE, Pierce M et al. A Phase 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals. Vaccine27(31), 4104–4109 (2009).
   PubMed Web of Science ®Google Scholar
• Casella CR, Mitchell TC. Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell. Mol. Life Sci.65(20), 3231–3240 (2008).
   PubMed Web of Science ®Google Scholar
• Roach JC, Glusman G, Rowen L et al. The evolution of vertebrate Toll-like receptors. Proc. Natl Acad. Sci. USA102(27), 9577–9582 (2005).
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. TLR signaling. Semin. Immunol.19(1), 24–32 (2007).
   PubMed Web of Science ®Google Scholar
• Leonard JN, Ghirlando R, Askins J et al. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc. Natl Acad. Sci. USA105(1), 258–263 (2008).
   PubMed Web of Science ®Google Scholar
• Jin MS, Kim SE, Heo JY et al. Crystal structure of the TLR1–TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell130(6), 1071–1082 (2007).
   PubMed Web of Science ®Google Scholar
• Kim HM, Park BS, Kim J-I et al. Crystal structure of the TLR4–MD-2 complex with bound endotoxin antagonist eritoran. Cell130(5), 906–917 (2007).
   PubMed Web of Science ®Google Scholar
• Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat. Rev. Immunol.9(8), 535–542 (2009).
   PubMed Web of Science ®Google Scholar
• Hasan U, Chaffois C, Gaillard C et al. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol.174(5), 2942–2950 (2005).
   PubMed Web of Science ®Google Scholar
• Schmidtke JR, Johnson AG. Regulation of the immune system by synthetic polynucleotides. I. Characteristics of adjuvant action on antibody synthesis. J. Immunol.106(5), 1191–1200 (1971).
   PubMed Web of Science ®Google Scholar
• Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol.2(8), 675–680 (2001).
   PubMed Web of Science ®Google Scholar
• Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol.5(10), 987–995 (2004).
   PubMed Web of Science ®Google Scholar
• Medzhitov R, Janeway CA Jr. Innate immune induction of the adaptive immune response. Cold Spring Harb. Symp. Quant. Biol.64, 429–435 (1999).
   PubMedGoogle Scholar
• Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol.5(10), 987–995 (2004).
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. Innate immune recognition of viral infection. Nat. Immunol.7(2), 131–137 (2006).
   PubMed Web of Science ®Google Scholar
• Kadowaki N, Ho S, Antonenko S et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med.194(6), 863–870 (2001).
   PubMed Web of Science ®Google Scholar
• Akira S, Takeda K. Toll-like receptor signalling. Nat. Rev. Immunol.4(7), 499–511 (2004).
   PubMed Web of Science ®Google Scholar
• O’Neill LAJ, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol.7(5), 353–364 (2007).
   PubMed Web of Science ®Google Scholar
• O’Neill LAJ. How Toll-like receptors signal: what we know and what we don’t know. Curr. Opin. Immunol.18(1), 3–9 (2006).
   PubMed Web of Science ®Google Scholar
• Shinobu N, Iwamura T, Yoneyama M et al. Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide. FEBS Lett.517(1–3), 251–256 (2002).
   PubMedGoogle Scholar
• Kenny EF, Talbot S, Gong M, Golenbock DT, Bryant CE, O’Neill LAJ. MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3. J. Immunol.183(6), 3642–3651 (2009).
   PubMed Web of Science ®Google Scholar
• Kawagoe T, Sato S, Matsushita K et al. Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2. Nat. Immunol.9(6), 684–691 (2008).
   PubMed Web of Science ®Google Scholar
• Yamamoto M, Sato S, Hemmi H et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol.4(11), 1144–1150 (2003).
   PubMed Web of Science ®Google Scholar
• Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J. Exp. Med.202(12), 1715–1724 (2005).
   PubMed Web of Science ®Google Scholar
• Sorensen LN, Reinert LS, Malmgaard L, Bartholdy C, Thomsen AR, Paludan SR. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J. Immunol.181(12), 8604–8612 (2008).
   PubMed Web of Science ®Google Scholar
• Bagchi A, Herrup EA, Warren HS et al. MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists. J. Immunol.178(2), 1164–1171 (2007).
   PubMed Web of Science ®Google Scholar
• Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochem. Biophys. Res. Commun.354(4), 1045–1051 (2007).
   PubMed Web of Science ®Google Scholar
• Zhu Q, Egelston C, Vivekanandhan A et al. Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines. Proc. Natl Acad. Sci. USA105(42), 16260–16265 (2008).
   PubMed Web of Science ®Google Scholar
• Ghosh TK, Mickelson DJ, Solberg JC, Lipson KE, Inglefield JR, Alkan SS. TLR-TLR cross talk in human PBMC resulting in synergistic and antagonistic regulation of type-1 and 2 interferons, IL-12 and TNF-α. Int. Immunopharmacol.7(8), 1111–1121 (2007).
   PubMed Web of Science ®Google Scholar
• Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat. Immunol.6(8), 769–776 (2005).
   PubMed Web of Science ®Google Scholar
• Warger T, Osterloh P, Rechtsteiner G et al. Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo. Blood108(2), 544–550 (2006).
   PubMed Web of Science ®Google Scholar
• Dan JM, Wang JP, Lee CK, Levitz SM. Cooperative stimulation of dendritic cells by Cryptococcus neoformans mannoproteins and CpG oligodeoxynucleotides. PLoS ONE3(4), e2046 (2008).
   PubMed Web of Science ®Google Scholar
• Dearman RJ, Cumberbatch M, Portsmouth C, Maxwell G, Basketter DA, Kimber I. Synergistic effects of chemical insult and toll-like receptor ligands on dendritic cell activation. Toxicol In Vitro22(8), 1927–1934 (2008).
   PubMed Web of Science ®Google Scholar
• Tada H, Aiba S, Shibata KI, Ohteki T, Takada H. Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper type 1 cells. Infect. Immun.73(12), 7967–7976 (2005).
   PubMed Web of Science ®Google Scholar
• Underhill DM. Collaboration between the innate immune receptors dectin-1, TLRs, and Nods. Immunol. Rev.219, 75–87 (2007).
   PubMed Web of Science ®Google Scholar
• Liew FY, Xu D, Brint EK, O’Neill LAJ. Negative regulation of Toll-like receptor-mediated immune responses. Nat. Rev. Immunol.5(6), 446–458 (2005).
   PubMed Web of Science ®Google Scholar
• O’Neill LAJ. Targeting signal transduction as a strategy to treat inflammatory diseases. Nat. Rev. Drug Discov.5(7), 549–563 (2006).
   PubMed Web of Science ®Google Scholar
• Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H. Role of Toll-like receptors in the development of sepsis. Shock29(3), 315–321 (2008).
   PubMed Web of Science ®Google Scholar
• Kohn LD, Wallace B, Schwartz F, McCall K. Is Type 2 diabetes an autoimmune-inflammatory disorder of the innate immune system? Endocrinology146(10), 4189–4191 (2005).
   PubMedGoogle Scholar
• Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. J. Lipid Res.50(Suppl.), S340–S345 (2009).
   PubMedGoogle Scholar
• O’Neill LAJ. When signaling pathways collide: positive and negative regulation of Toll-like receptor signal transduction. Immunity29(1), 12–20 (2008).
   PubMed Web of Science ®Google Scholar
• Ichikawa HT, Williams LP, Segal BM. Activation of APCs through CD40 or Toll-like receptor 9 overcomes tolerance and precipitates autoimmune disease. J. Immunol.169(5), 2781–2787 (2002).
   PubMed Web of Science ®Google Scholar
• Vaknin I, Blinder L, Wang L et al. A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression. Blood111(3), 1437–1447 (2008).
   PubMedGoogle Scholar
• Netea MG, Van der Meer JW, Kullberg BJ. Toll-like receptors as an escape mechanism from the host defense. Trends Microbiol.12(11), 484–488 (2004).
   PubMed Web of Science ®Google Scholar
• Gavin AL, Hoebe K, Duong B et al. Adjuvant-enhanced antibody responses in the absence of Toll-like receptor signaling. Science314(5807), 1936–1938 (2006).
   PubMed Web of Science ®Google Scholar
• Mutwiri GK, Nichani AK, Babiuk S, Babiuk LA. Strategies for enhancing the immunostimulatory effects of CpG oligodeoxynucleotides. J. Control Release97(1), 1–17 (2004).
   PubMed Web of Science ®Google Scholar
• Blander JM, Medzhitov R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature440(7085), 808–812 (2006).
   PubMed Web of Science ®Google Scholar
• Moyle PM, Toth I. Self-adjuvanting lipopeptide vaccines. Curr. Med. Chem.15(5), 506–516 (2008).
   PubMedGoogle Scholar
• Eriksson EMY, Jackson DC. Recent advances with TLR2-targeting lipopeptide-based vaccines. Curr. Protein Pept. Sci.8(4), 412–417 (2007).
   PubMed Web of Science ®Google Scholar
• Zeng W, Ghosh S, Lau YF, Brown LE, Jackson DC. Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J. Immunol.169(9), 4905–4912 (2002).
   PubMed Web of Science ®Google Scholar
• Chua BY, Zeng WG, Lau YF, Jackson DC. Comparison of lipopeptide-based immunocontraceptive vaccines containing different lipid groups. Vaccine25(1), 92–101 (2007).
   PubMed Web of Science ®Google Scholar
• Abdel-Aal ABM, Batzloff MR, Fujita Y et al. Structure–activity relationship of a series of synthetic lipopeptide self-adjuvanting group A streptococcal vaccine candidates. J. Med. Chem.51(1), 167–172 (2008).
   PubMedGoogle Scholar
• Tirrell M. Modular materials by self-assembly. AIChE J.51(9), 2386–2390 (2005).
   Google Scholar
• Zhang X, Chentoufi AA, Dasgupta G et al. A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge. Mucosal Immunol.2(2), 129–143 (2009).
   PubMed Web of Science ®Google Scholar
• Chua BY, Eriksson EM, Brown LE et al. A self-adjuvanting lipopeptide-based vaccine candidate for the treatment of hepatitis C virus infection. Vaccine26(37), 4866–4875 (2008).
   PubMed Web of Science ®Google Scholar
• Jackson DC, Lau YF, Le T et al. A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc. Natl Acad. Sci. USA101(43), 15440–15445 (2004).
   PubMed Web of Science ®Google Scholar
• Olive C, Batzloff M, Horvath A et al. Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens. Infect. Immun.71(5), 2373–2383 (2003).
   PubMed Web of Science ®Google Scholar
• Olive C, Ho MF, Dyer J et al. Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus. J. Infect. Dis.193(12), 1666–1676 (2006).
   PubMedGoogle Scholar
• Olive C, Schulze K, Sun HK et al. Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/SfbI lipid core peptide vaccine formulation. Vaccine25(10), 1789–1797 (2007).
   PubMed Web of Science ®Google Scholar
• Olive C, Sun Hsien K, Ho M-F et al. Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein. J. Infect. Dis.194(3), 316–324 (2006).
   PubMedGoogle Scholar
• Lbachir B, Yasmine B, Estelle L, Karima B, Helene G-M, Pierre D. Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant. Eur. J. Immunol.32(8), 2274–2281 (2002).
   PubMedGoogle Scholar
• Durier C, Launay O, Meiffredy V et al. Clinical safety of HIV lipopeptides used as vaccines in healthy volunteers and HIV-infected adults. AIDS20(7), 1039–1049 (2006).
   PubMed Web of Science ®Google Scholar
• Steller MA, Gurski KJ, Murakami M et al. Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7. Clin. Cancer Res.4(9), 2103–2109 (1998).
   PubMed Web of Science ®Google Scholar
• Wille-Reece U, Wu C-y, 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.174(12), 7676–7683 (2005).
   PubMed Web of Science ®Google Scholar
• Heit A, Schmitz F, O’Keeffe M et al. Protective CD8 T cell immunity triggered by CpG–protein conjugates competes with the efficacy of live vaccines. J. Immunol.174(7), 4373–4380 (2005).
   PubMed Web of Science ®Google Scholar
• Khan S, Bijker MS, Weterings JJ et al. Distinct uptake mechanisms but similar intracellular processing of two different Toll-like receptor ligand–peptide conjugates in dendritic cells. J. Biol. Chem.282(29), 21145–21159 (2007).
   PubMed Web of Science ®Google Scholar
• Cui ZR, Qiu F. Synthetic double-stranded RNA poly(I : C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model. Cancer Immunol. Immunother.55(10), 1267–1279 (2006).
   PubMed Web of Science ®Google Scholar
• Karmali PP, Kotamraju VR, Kastantin M et al. Targeting of albumin-embedded paclitaxel nanoparticles to tumors. Nanomedicine5(1), 73–82 (2008).
   PubMedGoogle Scholar
• Peters D, Kastantin M, Kotamraju VR et al. Targeting atherosclerosis by using modular, multifunctional micelles. Proc. Natl Acad. Sci. USA106(24), 9815–9819 (2009).
   PubMed Web of Science ®Google Scholar
• Keegan ME, Whittum-Hudson JA, Mark Saltzman W. Biomimetic design in microparticulate vaccines. Biomaterials24(24), 4435–4443 (2003).
   PubMed Web of Science ®Google Scholar
• Scheerlinck JP, Greenwood DL. Virus-sized vaccine delivery systems. Drug Discov. Today13(19–20), 882–887 (2008).
   PubMed Web of Science ®Google Scholar
• Xiang SD, Scholzen A, Minigo G et al. Pathogen recognition and development of particulate vaccines: does size matter? Methods40(1), 1–9 (2006).
   PubMed Web of Science ®Google Scholar
• Pelkmans L. Secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses. Biochim. Biophys. Acta1746(3), 295–304 (2005).
   PubMed Web of Science ®Google Scholar
• Mottram PL, Leong D, Crimeen-Irwin B et al. Type 1 and 2 immunity following vaccination is influenced by nanoparticle size: formulation of a model vaccine for respiratory syncytial virus. Mol. Pharm.4(1), 73–84 (2007).
   PubMed Web of Science ®Google Scholar
• Reddy ST, Berk DA, Jain RK, Swartz MA. A sensitive in vivo model for quantifying interstitial convective transport of injected macromolecules and nanoparticles. J. Appl. Physiol.101(4), 1162–1169 (2006).
   PubMed Web of Science ®Google Scholar
• Reddy ST, Rehor A, Schmoekel HG, Hubbell JA, Swartz MA. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. J. Control Release112(1), 26–34 (2006).
   PubMed Web of Science ®Google Scholar
• Oussoren C, Zuidema J, Crommelin DJ, Storm G. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection. II. Influence of liposomal size, lipid compostion and lipid dose. Biochim. Biophys. Acta1328(2), 261–272 (1997).
   PubMed Web of Science ®Google Scholar
• Fehr T, Skrastina D, Pumpens P, Zinkernagel RM. T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. Proc. Natl Acad. Sci. USA95(16), 9477–9481 (1998).
   PubMed Web of Science ®Google Scholar
• Ohno S, Kohyama S, Taneichi M et al. Synthetic peptides coupled to the surface of liposomes effectively induce SARS coronavirus-specific cytotoxic T lymphocytes and viral clearance in HLA-A*0201 transgenic mice. Vaccine27(29), 3912–3920 (2009).
   PubMed Web of Science ®Google Scholar
• Espuelas S, Roth A, Thumann C, Frisch B, Schuber F. Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells. Mol. Immunol.42(6), 721–729 (2005).
   PubMed Web of Science ®Google Scholar
• Steers NJ, Peachman KK, McClain S, Alving CR, Rao M. Liposome-encapsulated HIV-1 Gag p24 containing lipid A induces effector CD4+ T-cells, memory CD8+ T-cells, and pro-inflammatory cytokines. Vaccine27(49), 6939–6949 (2009).
   PubMed Web of Science ®Google Scholar
• Butts C, Murray N, Maksymiuk A et al. Randomized Phase IIB trial of BLP25 liposome vaccine in Stage IIIB and IV non-small-cell lung cancer. J. Clin. Oncol.23(27), 6674–6681 (2005).
   PubMed Web of Science ®Google Scholar
• Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non-small cell lung cancer. Clin. Cancer Res.13(15), 4652s–4654s (2007).
   PubMed Web of Science ®Google Scholar
• Zaks K, Jordan M, Guth A et al. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J. Immunol.176(12), 7335–7345 (2006).
   PubMed Web of Science ®Google Scholar
• Hornung V, Guenthner-Biller M, Bourquin C et al. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med.11(3), 263–270 (2005).
   PubMed Web of Science ®Google Scholar
• Kuramoto Y, Kawakami S, Zhou S, Fukuda K, Yamashita F, Hashida M. Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG DNA/cationic liposome complex in mice. J. Control Release126(3), 274–280 (2008).
   PubMedGoogle Scholar
• Johnston D, Zaidi B, Bystryn JC. TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines. Cancer Immunol. Immunother.56(8), 1133–1141 (2007).
   PubMed Web of Science ®Google Scholar
• Laing P, Bacon A, McCormack B, Gregoriadis G, Frisch Bt, Schuber F. The ‘co-delivery’ approach to liposomal vaccines: application to the development of influenza-A and hepatitis-B vaccine candidates. J. Liposome Res.16(3), 229–235 (2006).
   PubMed Web of Science ®Google Scholar
• De Oliveira MC, Boutet V, Fattal E et al. Improvement of in vivo stability of phosphodiester oligonucleotide using anionic liposomes in mice. Life Sci.67(13), 1625–1637 (2000).
   PubMed Web of Science ®Google Scholar
• Yu RZ, Geary RS, Leeds JM et al. Pharmacokinetics and tissue disposition in monkeys of an antisense oligonucleotide inhibitor of Ha-ras encapsulated in stealth liposomes. Pharm. Res.16(8), 1309–1315 (1999).
   PubMedGoogle Scholar
• Foged C, Arigita C, Sundblad A, Jiskoot W, Storm G, Frokjaer S. Interaction of dendritic cells with antigen-containing liposomes: effect of bilayer composition. Vaccine22(15–16), 1903–1913 (2004).
   PubMed Web of Science ®Google Scholar
• van Broekhoven CL, Parish CR, Demangel C, Britton WJ, Altin JG. Targeting dendritic cells with antigen-containing liposomes: a highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res.64(12), 4357–4365 (2004).
   PubMed Web of Science ®Google Scholar
• Yasuda K, Ogawa Y, Yamane I, Nishikawa M, Takakura Y. Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways. J. Leukoc. Biol.77(1), 71–79 (2005).
   PubMed Web of Science ®Google Scholar
• Belizaire R, Unanue ER. Targeting proteins to distinct subcellular compartments reveals unique requirements for MHC class I and II presentation. Proc. Natl Acad. Sci. USA106(41), 17463–17468 (2009).
   PubMed Web of Science ®Google Scholar
• Nakano Y, Mori M, Nishinohara S et al. Surface-linked liposomal antigen induces IgE-selective unresponsiveness regardless of the lipid components of liposomes. Bioconjug. Chem.12(3), 391–395 (2001).
   PubMed Web of Science ®Google Scholar
• Perrie Y, Frederik PM, Gregoriadis G. Liposome-mediated DNA vaccination: the effect of vesicle composition. Vaccine19(23–24), 3301–3310 (2001).
   PubMed Web of Science ®Google Scholar
• Taneichi M, Ishida H, Kajino K et al. Antigen chemically coupled to the surface of liposomes are cross-presented to CD8+ T cells and induce potent antitumor immunity. J. Immunol.177(4), 2324–2330 (2006).
   PubMed Web of Science ®Google Scholar
• Sprott GD, Dicaire CJ, Gurnani K, Deschatelets LA, Krishnan L. Liposome adjuvants prepared from the total polar lipids of Haloferax volcanii, Planococcus spp. and Bacillus firmus differ in ability to elicit and sustain immune responses. Vaccine22(17–18), 2154–2162 (2004).
   PubMedGoogle Scholar
• Rosenkrands I, Agger EM, Olsen AW et al. Cationic liposomes containing mycobacterial lipids: a new powerful Th1 adjuvant system. Infect. Immun.73(9), 5817–5826 (2005).
   PubMed Web of Science ®Google Scholar
• Lonez C, Vandenbranden M, Ruysschaert J-M. Cationic liposomal lipids: from gene carriers to cell signaling. Prog. Lipid Res.47(5), 340–347 (2008).
   PubMed Web of Science ®Google Scholar
• Vangasseri DP, Cui ZR, Chen WH, Hokey DA, Falo LD, Huang L. Immunostimulation of dendritic cells by cationic liposomes. Mol. Membr. Biol.23(5), 385–395 (2006).
   PubMed Web of Science ®Google Scholar
• Richards RL, Rao M, Wassef NM, Glenn GM, Rothwell SW, Alving CR. Liposomes containing lipid a serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen. Infect. Immun.66(6), 2859–2865 (1998).
   PubMed Web of Science ®Google Scholar
• Sun H-X, Xie Y, Ye Y-P. ISCOMs and ISCOMATRIX™. Vaccine27(33), 4388–4401 (2009).
   PubMed Web of Science ®Google Scholar
• Skene CD, Sutton P. Saponin-adjuvanted particulate vaccines for clinical use. Methods40(1), 53–59 (2006).
   PubMed Web of Science ®Google Scholar
• Morein B, Hu KF, Abusugra I. Current status and potential application of ISCOMs in veterinary medicine. Adv. Drug Deliv. Rev.56(10), 1367–1382 (2004).
   PubMed Web of Science ®Google Scholar
• de Gassart A, Geminard C, Fevrier B, Raposo G, Vidal M. Lipid raft-associated protein sorting in exosomes. Blood102(13), 4336–4344 (2003).
   PubMed Web of Science ®Google Scholar
• Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol.17(7), 879–887 (2005).
   PubMed Web of Science ®Google Scholar
• Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol.2(8), 569–579 (2002).
   PubMed Web of Science ®Google Scholar
• Montecalvo A, Shufesky WJ, Stolz DB et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J. Immunol.180(5), 3081–3090 (2008).
   PubMed Web of Science ®Google Scholar
• Aline F, Bout D, Amigorena S, Roingeard P, Dimier-Poisson I. Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect. Immun.72(7), 4127–4137 (2004).
   PubMed Web of Science ®Google Scholar
• Andre F, Chaput N, Schartz NE et al. Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J. Immunol.172(4), 2126–2136 (2004).
   PubMed Web of Science ®Google Scholar
• Chaput N, Schartz NE, Andre F et al. Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J. Immunol.172(4), 2137–2146 (2004).
   PubMed Web of Science ®Google Scholar
• Mignot G, Roux S, Thery C, Segura E, Zitvogel L. Prospects for exosomes in immunotherapy of cancer. J. Cell Mol. Med.10(2), 376–388 (2006).
   PubMed Web of Science ®Google Scholar
• Grgacic EV, Anderson DA. Virus-like particles: passport to immune recognition. Methods40(1), 60–65 (2006).
   PubMed Web of Science ®Google Scholar
• Herzog C, Hartmann K, Kunzi V et al. Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine27(33), 4381–4387 (2009).
   PubMed Web of Science ®Google Scholar
• Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J. Immunol.172(3), 1777–1785 (2004).
   PubMed Web of Science ®Google Scholar
• Wang BZ, Quan FS, Kang SM, Bozja J, Skountzou I, Compans RW. Incorporation of membrane-anchored flagellin into influenza virus-like particles enhances the breadth of immune responses. J. Virol.82(23), 11813–11823 (2008).
   PubMed Web of Science ®Google Scholar
• de Vries JJ, Bungener L, Ter Veer W et al. Incorporation of LpxL1, a detoxified lipopolysaccharide adjuvant, in influenza H5N1 virosomes increases vaccine immunogenicity. Vaccine27(6), 947–955 (2009).
   PubMedGoogle Scholar
• Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM. Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. J. Control Release125(3), 193–209 (2008).
   PubMed Web of Science ®Google Scholar
• Luzardo-Alvarez A, Blarer N, Peter K et al. Biodegradable microspheres alone do not stimulate murine macrophages in vitro, but prolong antigen presentation by macrophages in vitro and stimulate a solid immune response in mice. J. Control Release109(1–3), 62–76 (2005).
   PubMed Web of Science ®Google Scholar
• Thiele L, Rothen-Rutishauser B, Jilek S, Wunderli-Allenspach H, Merkle HP, Walter E. Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages? J. Control Release76(1–2), 59–71 (2001).
   PubMed Web of Science ®Google Scholar
• Kimberley DN, Praveen E, Glen SK, John S. Uptake of poly(d,l lactic-co-glycolic acid) microspheres by antigen-presenting cells in vivo. J. Biomed. Mater. Res.60(3), 480–486 (2002).
   PubMedGoogle Scholar
• Chong CS, Cao M, Wong WW et al. Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery. J. Control Release102(1), 85–99 (2005).
   PubMed Web of Science ®Google Scholar
• Wischke C, Zimmermann J, Wessinger B et al. Poly(I:C) coated PLGA microparticles induce dendritic cell maturation. Int. J. Pharm.365(1–2), 61–68 (2009).
   PubMed Web of Science ®Google Scholar
• Kazzaz J, Singh M, Ugozzoli M, Chesko J, Soenawan E, O’Hagan DT. Encapsulation of the immune potentiators MPL and RC529 in PLG microparticles enhances their potency. J. Control Release110(3), 566–573 (2006).
   PubMed Web of Science ®Google Scholar
• Chong S-F, Sexton A, De Rose R, Kent SJ, Zelikin AN, Caruso F. A paradigm for peptide vaccine delivery using viral epitopes encapsulated in degradable polymer hydrogel capsules. Biomaterials30(28), 5178–5186 (2009).
   PubMed Web of Science ®Google Scholar
• Greenwood DLV, Dynon K, Kalkanidis M, Xiang S, Plebanski M, Scheerlinck J-PY. Vaccination against foot-and-mouth disease virus using peptides conjugated to nano-beads. Vaccine26(22), 2706–2713 (2008).
   PubMed Web of Science ®Google Scholar
• Fifis T, Gamvrellis A, Crimeen-Irwin B et al. Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J. Immunol.173(5), 3148–3154 (2004).
   PubMed Web of Science ®Google Scholar
• Casella CR, Mitchell TC. Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell Mol. Life Sci.65(20), 3231–3240 (2008).
   PubMed Web of Science ®Google Scholar