Selection of adjuvants for vaccines targeting specific pathogens

References

• Roush SW, Murphy TV. Vaccine-Preventable Disease Table Working Group. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA. 2007;298(18):2155–2163.
   PubMed Web of Science ®Google Scholar
• Aoshi T. Modes of action for mucosal vaccine adjuvants. Viral Immunol. 2017;30(6):463–470.
   PubMed Web of Science ®Google Scholar
• Di Pasquale A, Preiss S, Tavares Da Silva F, et al. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines (Basel). 2015;3(2): 320–343.
   PubMed Web of Science ®Google Scholar
• Garcia A, De Sanctis JB. An overview of adjuvant formulations and delivery systems. APMIS. 2014;122(4):257–267.
   PubMed Web of Science ®Google Scholar
• Henriksen-Lacey M, Korsholm KS, Andersen P, et al. Liposomal vaccine delivery systems. Expert Opin Drug Deliv. 2011;8(4):505–519.
   PubMed Web of Science ®Google Scholar
• Schwendener RA. Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines. 2014;2(6):159–182.
   PubMedGoogle Scholar
• Sanders MT, Brown LE, Deliyannis G, et al. ISCOM-based vaccines: the second decade. Immunol Cell Biol. 2005;83(2):119–128.
   PubMed Web of Science ®Google Scholar
• Pearse MJ, Drane D. ISCOMATRIX adjuvant for antigen delivery. Adv Drug Deliv Rev. 2005;57(3):465–474.
   PubMed Web of Science ®Google Scholar
• Morelli AB, Becher D, Koernig S, et al. ISCOMATRIX: a novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases. J Med Microbiol. 2012;61(Pt 7):935–943.
   PubMed Web of Science ®Google Scholar
• Bigaeva E, Doorn E, Liu H, et al. Meta-analysis on randomized controlled trials of vaccines with qs-21 or iscomatrix adjuvant: safety and tolerability. PLoS One. 2016;11(5):e0154757.
   PubMed Web of Science ®Google Scholar
• Gregory AE, Titball R, Williamson D. Vaccine delivery using nanoparticles. Front Cell Infect Microbiol. 2013;3:13.
   PubMed Web of Science ®Google Scholar
• Flach TL, Ng G, Hari A, et al. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat Med. 2011;17(4):479–487.
   PubMed Web of Science ®Google Scholar
• De Gregorio E, Caproni E, Ulmer JB. Vaccine adjuvants: mode of action. Front Immunol. 2013;4:214.
   PubMed Web of Science ®Google Scholar
• Del Giudice G, Fragapane E, Bugarini R, et al. Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene. Clin Vaccine Immunol. 2006;13(9):1010–1013.
   PubMed Web of Science ®Google Scholar
• Garcon N, Di Pasquale A. From discovery to licensure, the adjuvant system story. Hum Vaccin Immunother. 2017;13(1):19–33.
   PubMed Web of Science ®Google Scholar
• Del Giudice G, Rappuoli R, Didierlaurent AM. Correlates of adjuvanticity: A review on adjuvants in licensed vaccines. Semin Immunol. 2018;39:14–21.
   PubMed Web of Science ®Google Scholar
• Ott G, Barchfeld GL, Chernoff D, et al. MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol. 19956(277–296).
   PubMedGoogle Scholar
• Cimica V, Boigard H, Bhatia B, et al. novel respiratory syncytial virus-like particle vaccine composed of the postfusion and prefusion conformations of the F glycoprotein. Clin Vaccine Immunol. 2016;23(6):451–459.
   PubMed Web of Science ®Google Scholar
• Apostolico Jde S, Lunardelli VA, Coirada FC, et al. Adjuvants: classification, modus operandi, and licensing. J Immunol Res. 2016;1459394:2016.
   Google Scholar
• Stephen J, Scales HE, Benson RA, et al. Neutrophil swarming and extracellular trap formation play a significant role in alum adjuvant activity. NPJ vaccines. 2017;2:1.
   PubMed Web of Science ®Google Scholar
• Nkolola JP, Cheung A, Perry JR, et al. Comparison of multiple adjuvants on the stability and immunogenicity of a clade C HIV-1 gp140 trimer. Vaccine. 2014;32(18):2109–2116.
   PubMed Web of Science ®Google Scholar
• Segal L, Wouters S, Morelle D, et al. Non-clinical safety and biodistribution of AS03-adjuvanted inactivated pandemic influenza vaccines. J Appl Toxicol. 2015;35(12):1564–1576.
   PubMed Web of Science ®Google Scholar
• Didierlaurent AM, Collignon C, Bourguignon P, et al. Enhancement of adaptive immunity by the human vaccine adjuvant AS01 depends on activated dendritic cells. J Immunol. 2014;193(4):1920–1930.
   PubMed Web of Science ®Google Scholar
• Lovgren Bengtsson K, Morein B, Osterhaus AD. ISCOM technology-based matrix M adjuvant: success in future vaccines relies on formulation. Expert Rev Vaccines. 2011;10(4):401–403.
   PubMed Web of Science ®Google Scholar
• Fox CB, Kramer RM, Barnes VL, et al. Working together: interactions between vaccine antigens and adjuvants. Ther Adv Vaccines. 2013;1(1):7–20.
   PubMedGoogle Scholar
• Querec T, Bennouna S, Alkan S, et al. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med. 2006;203(2):413–424.
   PubMed Web of Science ®Google Scholar
• Guan Y, Omueti-Ayoade K, Sk M, et al. Identification of novel synthetic toll-like receptor 2 agonists by high throughput screening. J Biol Chem. 2010;285(31):23755–23762.
   PubMed Web of Science ®Google Scholar
• Toussi DN, Massari P. Immune adjuvant effect of molecularly-defined toll-like receptor ligands. Vaccines (Basel). 2014;2(2):323–353.
   PubMedGoogle Scholar
• Paavonen J, Jenkins D, Bosch FX, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007;369(9580):2161–2170.
   PubMed Web of Science ®Google Scholar
• Kundi M. New hepatitis B vaccine formulated with an improved adjuvant system. Expert Rev Vaccines. 2007;6(2):133–140.
   PubMed Web of Science ®Google Scholar
• Fraillery D, Zosso N, Nardelli-Haefliger D. Rectal and vaginal immunization of mice with human papillomavirus L1 virus-like particles. Vaccine. 2009;27(17):2326–2334.
   PubMed Web of Science ®Google Scholar
• Kim YG. Microbiota influences vaccine and mucosal adjuvant efficacy. Immune Netw. 2017;17(1):20–24.
   PubMed Web of Science ®Google Scholar
• Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol. 2009;9(4):287–293.
   PubMed Web of Science ®Google Scholar
• Hayashi M, Aoshi T, Ozasa K, et al. RNA is an adjuvanticity mediator for the lipid-based mucosal adjuvant. Endocine Sci Rep. 2016;6:29165.
   PubMed Web of Science ®Google Scholar
• Carroll EC, Jin L, Mori A, et al. The vaccine adjuvant chitosan promotes cellular immunity via DNA sensor cGAS-STING-dependent induction of type I interferons. Immunity. 2016;44(3):597–608.
   PubMed Web of Science ®Google Scholar
• Christensen MH, Paludan SR. Viral evasion of DNA-stimulated innate immune responses. Cell Mol Immunol. 2017;14(1):4–13.
   PubMed Web of Science ®Google Scholar
• Blaauboer SM, Mansouri S, Tucker HR, et al. The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. eLife. 2015;4:E06670.
   PubMed Web of Science ®Google Scholar
• Petrovsky N, Cooper PD. Carbohydrate-based immune adjuvants. Expert Rev Vaccines. 2011;10(4):523–537.
   PubMed Web of Science ®Google Scholar
• Welsby I, Detienne S, N‘Kuli F, et al. Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21. Front Immunol. 2016;7:663.
   PubMed Web of Science ®Google Scholar
• Detienne S, Welsby I, Collignon C, et al. Central role of CD169(+) lymph node resident macrophages in the adjuvanticity of the QS-21 component of AS01. Sci Rep. 2016;6:39475.
   PubMed Web of Science ®Google Scholar
• Bergmann-Leitner ES, Leitner WW. Adjuvants in the driver‘s seat: how magnitude, type, fine specificity and longevity of immune responses are driven by distinct classes of immune potentiators. Vaccines (Basel). 2014;2(2):252–296.
   PubMedGoogle Scholar
• Didierlaurent AM, Morel S, Lockman L, et al. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol. 2009;183(10):6186–6197.
   PubMed Web of Science ®Google Scholar
• Cekic C, Casella CR, Eaves CA, et al. Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A. J Biol Chem. 2009;284(46):31982–31991.
   PubMed Web of Science ®Google Scholar
• Coccia M, Collignon C, Herve C, et al. Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNgamma response promoting vaccine immunogenicity. NPJ vaccines. 2017;2:25.
   PubMed Web of Science ®Google Scholar
• Leonard WJ, Wan CK. IL-21 Signaling in Immunity. F1000Res. 2016;5.
   PubMedGoogle Scholar
• Carter D, Fox CB, Day TA, et al. A structure-function approach to optimizing TLR4 ligands for human vaccines. Clin Transl Immunology. 2016;5(11):e108.
   PubMedGoogle Scholar
• Fang Y, Rowe T, Leon AJ, et al. Molecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus. J Virol. 2010;84(17):8369–8388.
   PubMed Web of Science ®Google Scholar
• Mastelic B, Ahmed S, Egan WM, et al. Mode of action of adjuvants: implications for vaccine safety and design. Biologicals. 2010;38(5):594–601.
   PubMedGoogle Scholar
• Mosaheb MM, Reiser ML, Wetzler LM. Toll-like receptor ligand-based vaccine adjuvants require intact myd88 signaling in antigen-presenting cells for germinal center formation and antibody production. Front Immunol. 2017;8:225.
   PubMed Web of Science ®Google Scholar
• Mosca F, Tritto E, Muzzi A et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA. 2008;105(30):10501–10506.
   PubMed Web of Science ®Google Scholar
• Seubert A, Monaci E, Pizza M, et al. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol. 2008;180(8):5402–5412.
   PubMed Web of Science ®Google Scholar
• Morel S, Didierlaurent A, Bourguignon P, et al. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine. 2011;29(13):2461–2473.
   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. 2008;205(4):869–882.
   PubMed Web of Science ®Google Scholar
• Windon RG, Chaplin PJ, Beezum L, et al. Induction of lymphocyte recruitment in the absence of a detectable immune response. Vaccine. 2000;19(4–5):572–578.
   PubMed Web of Science ®Google Scholar
• Sarkar I, Garg R, van Drunen Littel-van Den Hurk S. Formulation of the respiratory syncytial virus fusion protein with a polymer-based combination adjuvant promotes transient and local innate immune responses and leads to improved adaptive immunity. Vaccine. 2016;34(42):5114–5124.
   PubMed Web of Science ®Google Scholar
• Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12(6):509–517.
   PubMed Web of Science ®Google Scholar
• Burny W, Callegaro A, Bechtold V, et al. Different adjuvants induce common innate pathways that are associated with enhanced adaptive responses against a model antigen in humans. Front Immunol. 2017;8:943.
   PubMed Web of Science ®Google Scholar
• Givord C, Welsby I, Detienne S, et al. Activation of the endoplasmic reticulum stress sensor IRE1alpha by the vaccine adjuvant AS03 contributes to its immunostimulatory properties. NPJ vaccines. 2018;3:20.
   PubMed Web of Science ®Google Scholar
• Jordan MB, Mills DM, Kappler J, et al. Promotion of B cell immune responses via an alum-induced myeloid cell population. Science. 2004;304(5678):1808–1810.
   PubMed Web of Science ®Google Scholar
• Fuentes S, Klenow L, Golding H, et al. Preclinical evaluation of bacterially produced RSV-G protein vaccine: strong protection against RSV challenge in cotton rat model. Sci Rep. 2017;7:42428.
   PubMed Web of Science ®Google Scholar
• O‘Hagan DT, Friedland LR, Hanon E, et al. Towards an evidence based approach for the development of adjuvanted vaccines. Curr Opin Immunol. 2017;47:93–102.
   PubMed Web of Science ®Google Scholar
• Pulendran B, Oh JZ, Nakaya HI, et al. Immunity to viruses: learning from successful human vaccines. Immunol Rev. 2013;255(1):243–255.
   PubMed Web of Science ®Google Scholar
• Bentebibel SE, Lopez S, Obermoser G, et al. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med. 2013;5(176):176ra132.
   Web of Science ®Google Scholar
• Bjarnarson SP, Adarna BC, Benonisson H, et al. The adjuvant LT-K63 can restore delayed maturation of follicular dendritic cells and poor persistence of both protein- and polysaccharide-specific antibody-secreting cells in neonatal mice. J Immunol. 2012;189(3):1265–1273.
   PubMed Web of Science ®Google Scholar
• Ho NI, Huis In t Veld LGM, Raaijmakers TK, Adema GJ. Adjuvants enhancing cross-presentation by dendritic cells: the key to more effective vaccines? Front Immunol. 2018;9:2874.
   PubMed Web of Science ®Google Scholar
• Van Dis E, Sogi KM, Rae CS, et al. STING-activating adjuvants elicit a Th17 immune response and protect against Mycobacterium tuberculosis infection. Cell Rep. 2018;23(5):1435–1447.
   PubMed Web of Science ®Google Scholar
• Kamath AT, Rochat AF, Christensen D, et al. A liposome-based mycobacterial vaccine induces potent adult and neonatal multifunctional T cells through the exquisite targeting of dendritic cells. PloS one. 2009;4(6):e5771.
   PubMed Web of Science ®Google Scholar
• Madhun AS, Haaheim LR, Nostbakken JK, et al. Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice. Vaccine. 2011;29(31):4973–4982.
   PubMed Web of Science ®Google Scholar
• Kester KE, Cummings JF, Ofori-Anyinam O, et al. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J Infect Dis. 2009;200(3):337–346.
   PubMed Web of Science ®Google Scholar
• Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013;4:114.
   PubMed Web of Science ®Google Scholar
• Nijnik A, Madera L, Ma S, et al. Synthetic cationic peptide IDR-1002 provides protection against bacterial infections through chemokine induction and enhanced leukocyte recruitment. J Immunol. 2010;184(5):2539–2550.
   PubMed Web of Science ®Google Scholar
• Hatai H, Lepelley A, Zeng W, et al. 11 (TLR11) interacts with flagellin and profilin through disparate mechanisms. PLoS One. 2016;11(2):e0148987.
   PubMed Web of Science ®Google Scholar
• Shirota H, Tross D, Klinman DM. CpG oligonucleotides as cancer vaccine adjuvants. Vaccines (Basel). 2015;3(2):390–407.
   PubMed Web of Science ®Google Scholar
• Cui B, Liu X, Fang Y, et al. Flagellin as a vaccine adjuvant. Expert Rev Vaccines. 2018;17(4):335–349.
   PubMed Web of Science ®Google Scholar
• Kim SH, Jang YS. The development of mucosal vaccines for both mucosal and systemic immune induction and the roles played by adjuvants. Clin Exp Vaccine Res. 2017;6(1):15–21.
   PubMed Web of Science ®Google Scholar
• Risso GS, Carabajal MV, Bruno LA, et al. U-Omp19 from Brucella abortus is a useful adjuvant for vaccine formulations against salmonella infection in mice. Front Immunol. 2017;8:171.
   PubMed Web of Science ®Google Scholar
• Savelkoul HF, Ferro VA, Strioga MM, et al. Choice and design of adjuvants for parenteral and mucosal vaccines. Vaccines (Basel). 2015;3(1):148–171.
   PubMed Web of Science ®Google Scholar
• Graham BS. Vaccine development for respiratory syncytial virus. Curr Opin Virol. 2017;23:107–112.
   PubMed Web of Science ®Google Scholar
• Sastry M, Zhang B, Chen M, et al. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus. PLoS One. 2017;12(10):e0186854.
   PubMed Web of Science ®Google Scholar
• Garg R, Latimer L, Simko E, et al. van den Hurk S. Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation. J Gen Virol. 2014;95(Pt 2):301–306.
   PubMed Web of Science ®Google Scholar
• Zeng L. Mucosal adjuvants: opportunities and challenges. Hum Vaccin Immunother. 2016;12(9):2456–2458.
   PubMed Web of Science ®Google Scholar
• Belyakov IM, Ahlers JD. What role does the route of immunization play in the generation of protective immunity against mucosal pathogens? J Immunol. 2009;183(11):6883–6892.
   PubMed Web of Science ®Google Scholar
• Ichinohe T, Kawaguchi A, Tamura S, et al. Intranasal immunization with H5N1 vaccine plus poly I:poly C12U, a toll-like receptor agonist, protects mice against homologous and heterologous virus challenge. Microbes Infect. 2007;9(11):1333–1340.
   PubMed Web of Science ®Google Scholar
• Sharma S, Zhu L, Davoodi M, et al. TLR3 agonists and proinflammatory antitumor activities. Expert Opin Ther Targets. 2013;17(5):481–483.
   PubMed Web of Science ®Google Scholar
• Medeiros AI, Sa-Nunes A, Turato WM, et al. Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells. J Immunol. 2008;181(12):8544–8551.
   PubMed Web of Science ®Google Scholar
• Ferreira MU, Da Silva Nunes M, Wunderlich G. Antigenic diversity and immune evasion by malaria parasites. Clin Diagn Lab Immunol. 2004;11(6):987–995.
   PubMedGoogle Scholar
• Riley EM, Stewart VA. Immune mechanisms in malaria: new insights in vaccine development. Nat Med. 2013;19(2):168–178.
   PubMed Web of Science ®Google Scholar
• Newman MJ, Wu JY, Gardner BH, et al. Induction of cross-reactive cytotoxic T-lymphocyte responses specific for HIV-1 gp120 using saponin adjuvant (QS-21) supplemented subunit vaccine formulations. Vaccine. 1997;15(9):1001–1007.
   PubMed Web of Science ®Google Scholar
• Gosling R, von Seidlein L. The future of the rts,s/as01 malaria vaccine: an alternative development plan. PLoS Med. 2016;13(4):e1001994.
   PubMed Web of Science ®Google Scholar
• Martins KA, Bavari S, Salazar AM. Vaccine adjuvant uses of poly-IC and derivatives. Expert Rev Vaccines. 2015;14(3):447–459.
   PubMed Web of Science ®Google Scholar
• Dooling KL, Guo A, Patel M, et al. Recommendations of the advisory committee on immunization practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018;67(3):103–108.
   PubMed Web of Science ®Google Scholar
• Dendouga N, Fochesato M, Lockman L, et al. Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice. Vaccine. 2012;30(20):3126–3135.
   PubMed Web of Science ®Google Scholar
• Stanley M. HPV - immune response to infection and vaccination. Infect Agent Cancer. 2010;5:19.
   PubMedGoogle Scholar
• Haghshenas MR, Mousavi T, Kheradmand M, et al. Efficacy of human papillomavirus L1 protein vaccines (Cervarix and Gardasil) in reducing the risk of cervical intraepithelial neoplasia: a meta-analysis. Int J Prev Med. 2017;8:44.
   PubMed Web of Science ®Google Scholar
• Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol. 2008;109(2 Suppl):S15–21.
   PubMed Web of Science ®Google Scholar
• Leung TF, Liu AP, Lim FS, et al. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9–14 years: results to month 12 from a randomized trial. Hum Vaccin Immunother. 2015;11(7):1689–1702.
   PubMed Web of Science ®Google Scholar
• Moreno-Mendieta SA, Rocha-Zavaleta L, Rodriguez-Sanoja R. Adjuvants in tuberculosis vaccine development. FEMS Immunol Med Microbiol. 2010;58(1):75–84.
   PubMedGoogle Scholar
• Fletcher HA, Schrager L. TB vaccine development and the end tb strategy: importance and current status. Trans R Soc Trop Med Hyg. 2016;110(4):212–218.
   PubMed Web of Science ®Google Scholar
• Ferwerda G, Girardin SE, Kullberg BJ, et al. NOD2 and toll-like receptors are nonredundant recognition systems of mycobacterium tuberculosis. PLoS Pathog. 2005;1(3):279–285.
   PubMed Web of Science ®Google Scholar
• Khademi F, Derakhshan M, Yousefi-Avarvand A, et al. Multi-stage subunit vaccines against mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost? Expert Rev Vaccines. 2018;17(1):31–44.
   PubMed Web of Science ®Google Scholar
• Van Der Meeren O, Hatherill M, Nduba V, et al. Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. N Engl J Med. 2018;379(17):1621–1634.
   PubMed Web of Science ®Google Scholar
• Querec TD, Akondy RS, Lee EK, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10(1):116–125.
   PubMed Web of Science ®Google Scholar
• Nakaya HI, Wrammert J, Lee EK, et al. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011;12(8):786–795.
   PubMed Web of Science ®Google Scholar
• Vahey MT, Wang Z, Kester KE, et al. Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine. J Infect Dis. 2010;201(4):580–589.
   PubMed Web of Science ®Google Scholar
• Reif DM, Motsinger-Reif AA, McKinney BA, et al. Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination. Genes Immun. 2009;10(2):112–119.
   PubMed Web of Science ®Google Scholar
• Anderson J, Olafsdottir TA, Kratochvil S, et al. Molecular signatures of a TLR4 agonist-adjuvanted hiv-1 vaccine candidate in humans. Front Immunol. 2018;9:301.
   PubMed Web of Science ®Google Scholar
• Raeven RHM, Brummelman J, Pennings JLA, et al. Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination. Mucosal Immunol. 2018;11(3):979–993.
   Web of Science ®Google Scholar
• Rechtien A, Richert L, Lorenzo H, et al. Systems vaccinology identifies an early innate immune signature as a correlate of antibody responses to the ebola vaccine rVSV-ZEBOV. Cell Rep. 2017;20(9):2251–2261.
   PubMed Web of Science ®Google Scholar
• Mastelic B, Garcon N, Del Giudice G, et al. Predictive markers of safety and immunogenicity of adjuvanted vaccines. Biologicals. 2013;41(6):458–468.
   PubMed Web of Science ®Google Scholar
• Caproni E, Tritto E, Cortese M, et al. MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I-independent mechanism of action. J Immunol. 2012;188(7):3088–3098.
   PubMed Web of Science ®Google Scholar
• Tang H, Cao W, Kasturi SP, et al. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol. 2010;11(7):608–617.
   PubMed Web of Science ®Google Scholar
• Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19(12):1597–1608.
   PubMed Web of Science ®Google Scholar
• Kazmin D, Nakaya HI, Lee EK et al. Systems analysis of protective immune responses to RTS,S malaria vaccination in humans. Proc Natl Acad Sci USA. 2017;114(9):2425–2430.
   PubMed Web of Science ®Google Scholar
• Pulendran B, Li S, Nakaya HI. Systems vaccinology. Immunity. 2010;33(4):516–529.
   PubMed Web of Science ®Google Scholar
• Tomaras GD, Plotkin SA. Complex immune correlates of protection in HIV-1 vaccine efficacy trials. Immunol Rev. 2017;275(1):245–261.
   PubMed Web of Science ®Google Scholar
• Valletta JJ, Recker M. Identification of immune signatures predictive of clinical protection from malaria. PLoS Comput Biol. 2017;13(10):e1005812.
   PubMed Web of Science ®Google Scholar
• Hagan T, Nakaya HI, Subramaniam S, et al. Systems vaccinology: enabling rational vaccine design with systems biological approaches. Vaccine. 2015;33(40):5294–5301.
   PubMed Web of Science ®Google Scholar
• Furman D, Davis MM. New approaches to understanding the immune response to vaccination and infection. Vaccine. 2015;33(40):5271–5281.
   PubMed Web of Science ®Google Scholar
• Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010;33(4):492–503.
   PubMed Web of Science ®Google Scholar
• Baldwin SL, Bertholet S, Reese VA, et al. The importance of adjuvant formulation in the development of a tuberculosis vaccine. J Immunol. 2012;188(5):2189–2197.
   PubMed Web of Science ®Google Scholar
• Lee S, Nguyen MT. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw. 2015;15(2):51–57.
   PubMed Web of Science ®Google Scholar