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Neuroimmune Pharmacology pp 819–830Cite as

New Generation of Adjuvants for Protection Against Disease and to Combat Bioterrorism

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Abstract

This chapter highlights the characteristics of traditional and non-traditional adjuvants, the advantages and disadvantages of their use in vaccines. It has so served to introduce the concept of molecular and host-derived adjuvants to improve immune outcomes while minimizing toxicities. A particular emphasis was placed on the generation of conformationally-restricted, response-selective agonists of the complement component C5a. These all appear to have therapeutic, manufacturing, and commercial potential. However, the development and use of such molecular adjuvants for vaccines represent only one approach put forward to meet the modern-day threats posed by antibiotic-resistant strains of bacteria and bioterrorism. It is clear that a well-organized and concerted worldwide effort that utilizes multiple approaches to develop novel adjuvant and vaccine designs will be required to overcome these growing threats to human and animal populations.

Keywords

  • Antigen presenting cells
  • C5a
  • Complement
  • EP67
  • Molecular adjuvant
  • Vaccines

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References

  • Afonso LC, Scharton TM, Vieira LQ, Wysocka M, Trinchieri G, Scott P (1994) The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science 263(5144):235–237

    CrossRef  CAS  PubMed  Google Scholar 

  • Arvieux J, Yssel H, Colomb MG (1988) Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones. Immunology 65(2):229–235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Biragyn A, Tani K, Grimm MC, Weeks S, Kwak LW (1999) Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity. Nat Biotechnol 17(3):253–258. doi:10.1038/6995

    CrossRef  CAS  PubMed  Google Scholar 

  • Buchner RR, Hugli TE, Ember JA, Morgan EL (1995) Expression of functional receptors for human C5a anaphylatoxin (CD88) on the human hepatocellular carcinoma cell line HepG2. Stimulation of acute-phase protein-specific mRNA and protein synthesis by human C5a anaphylatoxin. J Immunol 155(1):308–315

    CAS  PubMed  Google Scholar 

  • Courtney AN (2010) Characterization of alpha-galactosylceramide as a mucosal adjuvant. Dissertation Thesis

    Google Scholar 

  • Crouch CF, Daly J, Henley W, Hannant D, Wilkins J, Francis MJ (2005) The use of a systemic prime/mucosal boost strategy with an equine influenza ISCOM vaccine to induce protective immunity in horses. Vet Immunol Immunopathol 108(3–4):345–355. doi:10.1016/j.vetimm.2005.06.009

    CrossRef  CAS  PubMed  Google Scholar 

  • Defoort JP, Nardelli B, Huang W, Tam JP (1992) A rational design of synthetic peptide vaccine with a built-in adjuvant. A modular approach for unambiguity. Int J Pept Protein Res 40(3–4):214–221

    CAS  PubMed  Google Scholar 

  • Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT (1996) C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271(5247):348–350

    CrossRef  CAS  PubMed  Google Scholar 

  • Diwan M, Elamanchili P, Cao M, Samuel J (2004) Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery. Curr Drug Deliv 1(4):405–412

    CrossRef  CAS  PubMed  Google Scholar 

  • Drapeau G, Brochu S, Godin D, Levesque L, Rioux F, Marceau F (1993) Synthetic C5a receptor agonists. Pharmacology, metabolism and in vivo cardiovascular and hematologic effects. Biochem Pharmacol 45(6):1289–1299

    CrossRef  CAS  PubMed  Google Scholar 

  • Duryee MJ, Bevins RA, Reichel CM, Murray JE, Dong Y, Thiele GM, Sanderson SD (2009) Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines. Vaccine 27(22):2981–2988. doi:10.1016/j.vaccine.2009.02.105

    CrossRef  CAS  PubMed  Google Scholar 

  • Ember JA, Sanderson SD, Hugli TE, Morgan EL (1994) Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin. Am J Pathol 144(2):393–403

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ember JA, Sanderson SD, Taylor SM, Kawahara M, Hugli TE (1992) Biologic activity of synthetic analogues of C5a anaphylatoxin. J Immunol 148(10):3165–3173

    CAS  PubMed  Google Scholar 

  • Finch AM, Vogen SM, Sherman SA, Kirnarsky L, Taylor SM, Sanderson SD (1997) Biologically active conformer of the effector region of human C5a and modulatory effects of N-terminal receptor binding determinants on activity. J Med Chem 40(6):877–884. doi:10.1021/jm960727r

    CrossRef  CAS  PubMed  Google Scholar 

  • Floreani AA, Gunselman SJ, Heires AJ, Hauke RJ, Tarantolo S, Jackson JD (2007) Novel C5a agonist-based dendritic cell vaccine in a murine model of melanoma. Cell Cycle 6(22):2835–2839

    CrossRef  CAS  PubMed  Google Scholar 

  • Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, Morgan EL, Sanderson SD (1998) Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke. J Immunol 160(10):5073–5081

    CAS  PubMed  Google Scholar 

  • Gasque P, Chan P, Fontaine M, Ischenko A, Lamacz M, Gotze O, Morgan BP (1995) Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes. J Immunol 155(10):4882–4889

    CAS  PubMed  Google Scholar 

  • Goldstein BD, Lai LY, Cuzzi-Spada R (1974) Potentiation of complement-dependent membrane damage by ozone. Arch Environ Health 28(1):40–42

    CrossRef  CAS  PubMed  Google Scholar 

  • Goodman MG, Chenoweth DE, Weigle WO (1982) Induction of interleukin 1 secretion and enhancement of humoral immunity by binding of human C5a to macrophage surface C5a receptors. J Exp Med 156(3):912–917

    CrossRef  CAS  PubMed  Google Scholar 

  • Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T (2013) Targeting macrophage activation for the prevention and treatment of Staphylococcus aureus biofilm infections. J Immunol 190(5):2159–2168. doi:10.4049/jimmunol.1202348

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Hegde GV, Meyers-Clark E, Joshi SS, Sanderson SD (2008) A conformationally-biased, response-selective agonist of C5a acts as a molecular adjuvant by modulating antigen processing and presentation activities of human dendritic cells. Int Immunopharmacol 8(6):819–827. doi:10.1016/j.intimp.2008.01.031

    CrossRef  CAS  PubMed  Google Scholar 

  • Hruby VJ, Prakash O, Kazmierski W, Gehrig C, Matsunaga TO (1991) Conformational analysis of opioid receptor-selective peptides using nuclear magnetic resonance and theoretical calculations. NIDA Res Monogr 112:198–217

    CAS  PubMed  Google Scholar 

  • Huang CF, Wu TC, Chu YH, Hwang KS, Wang CC, Peng HJ (2008) Effect of neonatal sublingual vaccination with native or denatured ovalbumin and adjuvant CpG or cholera toxin on systemic and mucosal immunity in mice. Scand J Immunol 68(5):502–510. doi:10.1111/j.1365-3083.2008.02172.x

    CrossRef  CAS  PubMed  Google Scholar 

  • Hugli TE (1981) The structural basis for anaphylatoxin and chemotactic functions of C3a, C4a, and C5a. Crit Rev Immunol 1(4):321–366

    CAS  PubMed  Google Scholar 

  • Hugli TE (1990) Structure and function of C3a anaphylatoxin. Curr Top Microbiol Immunol 153:181–208

    CAS  PubMed  Google Scholar 

  • Hugli TE, Gerard C, Kawahara M, Scheetz ME 2nd, Barton R, Briggs S, Koppel G, Russell S (1981) Isolation of three separate anaphylatoxins from complement-activated human serum. Mol Cell Biochem 41:59–66

    CrossRef  CAS  PubMed  Google Scholar 

  • Hugli TE, Marceau F, Lundberg C (1987) Effects of complement fragments on pulmonary and vascular smooth muscle. Am Rev Respir Dis 135(6 Pt 2):S9–S13

    CAS  PubMed  Google Scholar 

  • Hugli TE, Muller-Eberhard HJ (1978) Anaphylatoxins: C3a and C5a. Adv Immunol 26:1–53

    CrossRef  CAS  PubMed  Google Scholar 

  • Hung CY, Hurtgen BJ, Bellecourt M, Sanderson SD, Morgan EL, Cole GT (2012) An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. Vaccine 30(31):4681–4690. doi:10.1016/j.vaccine.2012.04.084

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacquier-Sarlin MR, Gabert FM, Villiers MB, Colomb MG (1995) Modulation of antigen processing and presentation by covalently linked complement C3b fragment. Immunology 84(1):164–170

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson AG, Gaines S, Landy M (1956) Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. J Exp Med 103(2):225–246

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson AR, Hugli TE, Muller-Eberhard HJ (1975) Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology 28(6):1067–1080

    CAS  PubMed  PubMed Central  Google Scholar 

  • Karuturi BVK (2014) Development of EP67-based mucosal vaccines against cytomegalovirus infection. Ph.D. Dissertation, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center

    Google Scholar 

  • Kawamoto S, Yalcindag A, Laouini D, Brodeur S, Bryce P, Lu B, Humbles AA, Oettgen H, Gerard C, Geha RS (2004) The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest 114(3):399–407. doi:10.1172/JCI19082

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim AH, Dimitriou ID, Holland MC, Mastellos D, Mueller YM, Altman JD, Lambris JD, Katsikis PD (2004) Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses. J Immunol 173(4):2524–2529

    CrossRef  CAS  PubMed  Google Scholar 

  • Kollessery G, Nordgren TM, Mittal AK, Joshi SS, Sanderson SD (2011) Tumor-specific peptide-based vaccines containing the conformationally biased, response-selective C5a agonists EP54 and EP67 protect against aggressive large B cell lymphoma in a syngeneic murine model. Vaccine 29(35):5904–5910. doi:10.1016/j.vaccine.2011.06.070

    CrossRef  CAS  PubMed  Google Scholar 

  • Kurzawa H, Wysocka M, Aruga E, Chang AE, Trinchieri G, Lee WM (1998) Recombinant interleukin 12 enhances cellular immune responses to vaccination only after a period of suppression. Cancer Res 58(3):491–499

    CAS  PubMed  Google Scholar 

  • Li K, Fazekasova H, Wang N, Peng Q, Sacks SH, Lombardi G, Zhou W (2012) Functional modulation of human monocytes derived DCs by anaphylatoxins C3a and C5a. Immunobiology 217(1):65–73. doi:10.1016/j.imbio.2011.07.033

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Lundberg C, Gardinali M, Hugli TE (1987) Complement activation and membrane lipids in lung vascular injury. Am Rev Respir Dis 136(2):459–462. doi:10.1164/ajrccm/136.2.459

    CrossRef  CAS  PubMed  Google Scholar 

  • Lycke N (2005) Targeted vaccine adjuvants based on modified cholera toxin. Curr Mol Med 5(6):591–597

    CrossRef  CAS  PubMed  Google Scholar 

  • Lycke N (2012) Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol 12(8):592–605. doi:10.1038/nri3251

    CrossRef  CAS  PubMed  Google Scholar 

  • Martinon F, Gras-Masse H, Boutillon C, Chirat F, Deprez B, Guillet JG, Gomard E, Tartar A, Levy JP (1992) Immunization of mice with lipopeptides bypasses the prerequisite for adjuvant. Immune response of BALB/c mice to human immunodeficiency virus envelope glycoprotein. J Immunol 149(10):3416–3422

    CAS  PubMed  Google Scholar 

  • Mastellos D, Germenis AE, Lambris JD (2005) Complement: an inflammatory pathway fulfilling multiple roles at the interface of innate immunity and development. Curr Drug Targets Inflamm Allergy 4(1):125–127

    CrossRef  CAS  PubMed  Google Scholar 

  • Metzger J, Wiesmuller KH, Schaude R, Bessler WG, Jung G (1991) Synthesis of novel immunologically active tripalmitoyl-S-glycerylcysteinyl lipopeptides as useful intermediates for immunogen preparations. Int J Pept Protein Res 37(1):46–57

    CrossRef  CAS  PubMed  Google Scholar 

  • Misicka A, Lipkowski AW, Fang L, Knapp RJ, Davis P, Kramer T, Burks TF, Yamamura HI, Carr DB, Hruby VJ (1991) Topographical requirements for delta opioid ligands: presence of a carboxyl group in position 4 is not critical for deltorphin high delta receptor affinity and analgesic activity. Biochem Biophys Res Commun 180(3):1290–1297

    CrossRef  CAS  PubMed  Google Scholar 

  • Mollison KW, Mandecki W, Zuiderweg ER, Fayer L, Fey TA, Krause RA, Conway RG, Miller L, Edalji RP, Shallcross MA et al (1989) Identification of receptor-binding residues in the inflammatory complement protein C5a by site-directed mutagenesis. Proc Natl Acad Sci U S A 86(1):292–296

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan EL (1986) Modulation of the immune response by anaphylatoxins. Complement 3(3):128–136

    CAS  PubMed  Google Scholar 

  • Morgan EL, Morgan BN, Stein EA, Vitrs EL, Thoman ML, Sanderson SD, Phillips JA (2009) Enhancement of in vivo and in vitro immune functions by a conformationally biased, response-selective agonist of human C5a: implications for a novel adjuvant in vaccine design. Vaccine 28(2):463–469. doi:10.1016/j.vaccine.2009.10.029

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan EL, Sanderson S, Scholz W, Noonan DJ, Weigle WO, Hugli TE (1992) Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. J Immunol 148(12):3937–3942

    CAS  PubMed  Google Scholar 

  • Morgan EL, Thoman ML, Sanderson SD, Phillips JA (2010) A novel adjuvant for vaccine development in the aged. Vaccine 28(52):8275–8279. doi:10.1016/j.vaccine.2010.10.008

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan EL, Thoman ML, Weigle WO, Hugli TE (1983) Anaphylatoxin-mediated regulation of the immune response. II. C5a-mediated enhancement of human humoral and T cell-mediated immune responses. J Immunol 130(3):1257–1261

    CAS  PubMed  Google Scholar 

  • Moulton RA, Mashruwala MA, Smith AK, Lindsey DR, Wetsel RA, Haviland DL, Hunter RL, Jagannath C (2007) Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice. J Leukoc Biol 82(4):956–967. doi:10.1189/jlb.0206119

    CrossRef  CAS  PubMed  Google Scholar 

  • Muhlradt PF, Kiess M, Meyer H, Sussmuth R, Jung G (1998) Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis. Infect Immun 66(10):4804–4810

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ochsenbein AF, Riddell SR, Brown M, Corey L, Baerlocher GM, Lansdorp PM, Greenberg PD (2004) CD27 expression promotes long-term survival of functional effector-memory CD8+ cytotoxic T lymphocytes in HIV-infected patients. J Exp Med 200(11):1407–1417. doi:10.1084/jem.20040717

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Okusawa S, Dinarello CA, Yancey KB, Endres S, Lawley TJ, Frank MM, Burke JF, Gelfand JA (1987) C5a induction of human interleukin 1. Synergistic effect with endotoxin or interferon-gamma. J Immunol 139(8):2635–2640

    CAS  PubMed  Google Scholar 

  • Olive C, Toth I, Jackson D (2001) Technological advances in antigen delivery and synthetic peptide vaccine developmental strategies. Mini Rev Med Chem 1(4):429–438

    CrossRef  CAS  PubMed  Google Scholar 

  • Pisarev VM, Kirnarsky L, Caffrey T, Hanisch F-G, Sanderson SD, Hollingsworth MA, Sherman S (2005) T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Int Immunopharmacol 5:315–330

    Google Scholar 

  • Phillips JA, Morgan EL, Dong Y, Cole GT, McMahan C, Hung CY, Sanderson SD (2009) Single-step conjugation of bioactive peptides to proteins via a self-containing succinimidyl bis-arylhydrazone. Bioconjug Chem 20:1950–1957

    Google Scholar 

  • Pobanz JM, Reinhardt RA, Koka S, Sanderson SD (2000) C5a modulation of interleukin-1 beta-induced interleukin-6 production by human osteoblast-like cells. J Periodontal Res 35(3):137–145

    CrossRef  CAS  PubMed  Google Scholar 

  • Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11(9):785–797. doi:10.1038/ni.1923

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudilla F, Fayolle C, Casares N, Durantez M, Arribillaga L, Lozano T, Villanueva L, Pio R, Sarobe P, Leclerc C, Prieto J, Lasarte JJ (2012) Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen-specific cytotoxic T cell responses. Vaccine 30(18):2848–2858. doi:10.1016/j.vaccine.2012.02.052

    CrossRef  CAS  PubMed  Google Scholar 

  • Sanderson SD, Cheruku SR, Padmanilayam MP, Vennerstrom JL, Thiele GM, Palmatier MI, Bevins RA (2003) Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant. Int Immunopharmacol 3(1):137–146

    CrossRef  CAS  PubMed  Google Scholar 

  • Sanderson SD, Thoman ML, Kis K, Virts EL, Herrera EB, Widmann S, Sepulveda H, Phillips JA (2012) Innate immune induction and influenza protection elicited by a response-selective agonist of human C5a. PLoS One 7(7), e40303. doi:10.1371/journal.pone.0040303

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  • Scholz W, McClurg MR, Cardenas GJ, Smith M, Noonan DJ, Hugli TE, Morgan EL (1990) C5a-mediated release of interleukin 6 by human monocytes. Clin Immunol Immunopathol 57(2):297–307

    CrossRef  CAS  PubMed  Google Scholar 

  • Schorlemmer HU, Davies P, Allison AC (1976) Ability of activated complement components to induce lysosomal enzyme release from macrophages. Nature 261(5555):48–49

    CrossRef  CAS  PubMed  Google Scholar 

  • Shi B, Tang P, Hu X, Liu JO, Yu B (2005) OSW saponins: facile synthesis toward a new type of structures with potent antitumor activities. J Org Chem 70(25):10354–10367. doi:10.1021/jo051536b

    CrossRef  CAS  PubMed  Google Scholar 

  • Shin HS, Snyderman R, Friedman E, Mellors A, Mayer MM (1968) Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement. Science 162(3851):361–363

    CrossRef  CAS  PubMed  Google Scholar 

  • Taylor SM, Sherman SA, Kirnarsky L, Sanderson SD (2001) Development of response-selective agonists of human C5a anaphylatoxin: conformational, biological, and therapeutic considerations. Curr Med Chem 8:675–684

    Google Scholar 

  • Tempero RM, Hollingsworth MA, Burdick MD, Finch AM, Taylor SM, Vogen SM, Morgan EL, Sanderson SD (1997) Molecular adjuvant effects of a conformationally biased agonist of human C5a anaphylatoxin. J Immunol 158(3):1377–1382

    CAS  PubMed  Google Scholar 

  • Tsuji NM, Kosaka A (2008) Oral tolerance: intestinal homeostasis and antigen-specific regulatory T cells. Trends Immunol 29(11):532–540. doi:10.1016/j.it.2008.09.002

    CrossRef  CAS  PubMed  Google Scholar 

  • Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (2000) Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant. J Immunol 164(10):5492–5498

    CrossRef  CAS  PubMed  Google Scholar 

  • Ulrich JT, Myers KR (1995) Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. Pharm Biotechnol 6:495–524

    CrossRef  CAS  PubMed  Google Scholar 

  • Vajdy M, Lycke NY (1992) Cholera toxin adjuvant promotes long-term immunological memory in the gut mucosa to unrelated immunogens after oral immunization. Immunology 75(3):488–492

    CAS  PubMed  PubMed Central  Google Scholar 

  • van Ginkel FW, Jackson RJ, Yoshino N, Hagiwara Y, Metzger DJ, Connell TD, Vu HL, Martin M, Fujihashi K, McGhee JR (2005) Enterotoxin-based mucosal adjuvants alter antigen trafficking and induce inflammatory responses in the nasal tract. Infect Immun 73(10):6892–6902. doi:10.1128/IAI.73.10.6892-6902.2005

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Vogen SM, Packowski N, Kirnarsky L, Sherman SA, Taylor SM, Sanderson SD (2001) Differential activities of decapeptide agonists of human C5a: the conformational effects of backbone N-methylation. Int Immunopharmacol 1:2151–2162

    Google Scholar 

  • Vogen SM, Prakash O, Kirnarsky L, Sanderson SD, Sherman SA (1999) Determination of structural elements related to the biological activities of a potent decapeptide agonist of human C5a anaphylatoxin. J Pept Res 54(1):74–84

    CrossRef  CAS  PubMed  Google Scholar 

  • Wetsel RA (1995a) Expression of the complement C5a anaphylatoxin receptor (C5aR) on non-myeloid cells. Immunol Lett 44(2–3):183–187

    CrossRef  CAS  PubMed  Google Scholar 

  • Wetsel RA (1995b) Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol 7(1):48–53

    CrossRef  CAS  PubMed  Google Scholar 

  • Wiesmuller KH, Bessler WG, Jung G (1992) Solid phase peptide synthesis of lipopeptide vaccines eliciting epitope-specific B-, T-helper and T-killer cell response. Int J Pept Protein Res 40(3–4):255–260

    CAS  PubMed  Google Scholar 

  • Xiao Y, Peperzak V, Keller AM, Borst J (2008) CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization. J Immunol 181(2):1071–1082

    CrossRef  CAS  PubMed  Google Scholar 

  • Zaal A, Lissenberg-Thunnissen SN, van Schijndel G, Wouters D, van Ham SM, ten Brinke A (2013) Crosstalk between Toll like receptors and C5a receptor in human monocyte derived DCs suppress inflammatory cytokine production. Immunobiology 218(2):175–180. doi:10.1016/j.imbio.2012.02.014

    CrossRef  CAS  PubMed  Google Scholar 

  • Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW (1989) Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data. Biochemistry 28(1):172–185

    CrossRef  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Sam D. Sanderson & Joseph A. Vetro

  2. Mylan Pharmaceuticals, Morgantown, WV, USA

    Bala Vamsi Krishna Karuturi

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  1. Sam D. Sanderson
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  2. Joseph A. Vetro
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  3. Bala Vamsi Krishna Karuturi
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Correspondence to Sam D. Sanderson .

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  1. Departments of Pharmacology and Experimental Therapeutics and Neurology, Boston University School of Medicine, Boston, Massachusetts, USA

    Tsuneya Ikezu

  2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Nebraska Medical Center, Omaha, Nebraska, USA

    Howard E. Gendelman

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Sanderson, S.D., Vetro, J.A., Karuturi, B.V.K. (2017). New Generation of Adjuvants for Protection Against Disease and to Combat Bioterrorism. In: Ikezu, T., Gendelman, H. (eds) Neuroimmune Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-44022-4_48

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