Adjuvanted influenza vaccines

References

• Glenny AT, Pope CG, Waddington H, Wallace U. Immunological notes. XVII–XXIV. J Pathol Bacteriol. 1926;29:31–40. doi:10.1002/path.1700290106.
   Google Scholar
• WHO. WHO | Influenza (Seasonal fact sheet). WHO: World Health Organization, 2016. http://www.who.int/mediacentre/factsheets/fs211/en/
   Google Scholar
• Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25:5086–96. doi:10.1016/j.vaccine.2007.03.046. PMID:17544181.
   PubMed Web of Science ®Google Scholar
• Preaud E, Durand L, Macabeo B, Farkas N, Sloesen B, Palache A, et al. Annual public health and economic benefits of seasonal influenza vaccination: a European estimate. BMC Public Health. 2014;14:813. doi:10.1186/1471-2458-14-813. PMID:25103091.
   PubMed Web of Science ®Google Scholar
• Beyer WEP, Nauta JJP, Palache AM, Giezeman KM, Osterhaus ADME. Immunogenicity and safety of inactivated influenza vaccines in primed populations: A systematic literature review and meta-analysis. Vaccine. 2011;29:5785–92. doi:10.1016/j.vaccine.2011.05.040. PMID:21624411.
   PubMed Web of Science ®Google Scholar
• Sarsenbayeva G, Volgin Y, Kassenov M, Issagulov T, Bogdanov N, Sansyzbay A, et al. Safety and immunogenicity of the novel seasonal preservative- and adjuvant-free influenza vaccine: Blind, randomized, and placebo-controlled trial. J Med Virol. 2017. doi:10.1002/jmv.24771.
   Web of Science ®Google Scholar
• Choi WS, Noh JY, Lee J, Choi JY, Lee JS, Kim MS, et al. Immunogenicity and safety of a split-virion quadrivalent influenza vaccine in adults 18-60 years of age in the Republic of Korea. Human vaccines & immunotherapeutics. 2017;0. Doi:10.1080/21645515.2017.1381808
   PubMed Web of Science ®Google Scholar
• Montalban C, Montellano MB, Santos J, Lavis N. Immunogenicity and safety of the 2015 Southern Hemisphere formulation of a split-virion inactivated quadrivalent vaccine. Human Vaccines & Immunotherapeutics. 2017:0. Doi:10.1080/21645515.2017.1377378
   PubMed Web of Science ®Google Scholar
• Latreille-Barbier M, Rouzier R, Astruc B, Lavis N, Donazzolo Y. Immunogenicity and safety of the southern hemisphere 2015 formulation of Vaxigrip(R). Human Vaccines & Immunotherapeutics. 2017:0.
   PubMed Web of Science ®Google Scholar
• Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg. 1972;70:767–77. doi:10.1017/S0022172400022610. PMID:4509641.
   PubMedGoogle Scholar
• Belongia EA, Kieke BA, Donahue JG, Greenlee RT, Balish A, Foust A, et al. Effectiveness of inactivated influenza vaccines varied substantially with antigenic match from the 2004–2005 season to the 2006–2007 season. J Infect Dis. 2009;199:159–67. doi:10.1086/595861. PMID:19086915.
   PubMed Web of Science ®Google Scholar
• Treanor JJ, Talbot HK, Ohmit SE, Coleman LA, Thompson MG, Cheng PY, et al. Effectiveness of seasonal influenza vaccines in the United States during a season with circulation of all three vaccine strains. Clin Infect Dis. 2012;55:951–9. doi:10.1093/cid/cis574. PMID:22843783.
   PubMed Web of Science ®Google Scholar
• Xie H, Wan XF, Ye Z, Plant EP, Zhao Y, Xu Y, et al. H3N2 Mismatch of 2014–15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps. Sci Rep. 2015;5:15279. doi:10.1038/srep15279. PMID:26472175.
   PubMed Web of Science ®Google Scholar
• Tricco AC, Chit A, Soobiah C, Hallett D, Meier G, Chen MH, et al. Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC Med. 2013;11:153. doi:10.1186/1741-7015-11-153. PMID:23800265.
   PubMed Web of Science ®Google Scholar
• Flannery B, Clippard J, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, et al. Early estimates of seasonal influenza vaccine effectiveness – United States, January 2015. MMWR Morb Mortal Wkly Rep. 2015;64:10–5. PMID:25590680.
   PubMed Web of Science ®Google Scholar
• Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada's Sentinel Physician Surveillance Network, January 2015. Euro Surveill. 2015;20.
   Google Scholar
• Yam KK, Gipson E, Klein M, Walmsley S, Haase D, Halperin S, et al. High level antibody avidity is achieved in HIV-seropositive recipients of an inactivated split adjuvanted (AS03A) influenza vaccine. J Clin Immunol. 2014;34:655–62. doi:10.1007/s10875-014-0054-z. PMID:24824648.
   PubMed Web of Science ®Google Scholar
• Dikow R, Eckerle I, Ksoll-Rudek D, Hampel H, Schwenger V, Zeier M, et al. Immunogenicity and efficacy in hemodialysis patients of an AS03(A)-adjuvanted vaccine for 2009 pandemic influenza A(H1N1): A nonrandomized trial. Am J Kidney Dis. 2011;57:716–23. doi:10.1053/j.ajkd.2010.11.031. PMID:21349617.
   PubMed Web of Science ®Google Scholar
• Siegrist CA, Aspinall R. B-cell responses to vaccination at the extremes of age. Nat Rev Immunol. 2009;9:185–94. doi:10.1038/nri2508. PMID:19240757.
   PubMed Web of Science ®Google Scholar
• Lafond KE, Nair H, Rasooly MH, Valente F, Booy R, Rahman M, et al. Global role and burden of influenza in pediatric respiratory hospitalizations, 1982–2012: A systematic analysis. PLoS Med. 2016;13:e1001977. doi:10.1371/journal.pmed.1001977. PMID:27011229.
   PubMed Web of Science ®Google Scholar
• Nolan T, Bravo L, Ceballos A, Mitha E, Gray G, Quiambao B, et al. Enhanced and persistent antibody response against homologous and heterologous strains elicited by a MF59-adjuvanted influenza vaccine in infants and young children. Vaccine. 2014;32:6146–56. doi:10.1016/j.vaccine.2014.08.068. PMID:25223266.
   PubMed Web of Science ®Google Scholar
• Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng P-Y, Steiner C, et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993–2008. Clin Infect Dis. 2012;54:1427–36. doi:10.1093/cid/cis211. PMID:22495079.
   PubMed Web of Science ®Google Scholar
• Yang WH, Dionne M, Kyle M, Aggarwal N, Li P, Madariaga M, et al. Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: An observer-blind, randomized trial. Vaccine. 2013;31:4389–97. doi:10.1016/j.vaccine.2013.07.007. PMID:23856331.
   PubMed Web of Science ®Google Scholar
• Frey SE, Reyes MR, Reynales H, Bermal NN, Nicolay U, Narasimhan V, et al. Comparison of the safety and immunogenicity of an MF59(R)-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 2014;32:5027–34. doi:10.1016/j.vaccine.2014.07.013. PMID:25045825.
   PubMed Web of Science ®Google Scholar
• Conne P, Gauthey L, Vernet P, Althaus B, Que JU, Finkel B, et al. Immunogenicity of trivalent subunit versus virosome-formulated influenza vaccines in geriatric patients. Vaccine. 1997;15:1675–9. doi:10.1016/S0264-410X(97)00087-X. PMID:9364699.
   PubMed Web of Science ®Google Scholar
• Dormitzer PR, Rappuoli R, Casini D, O'Hagan D, Runham C, Montomoli E, et al. Adjuvant is necessary for a robust immune response to a single dose of H1N1 pandemic flu vaccine in mice. PLoS Curr. 2009;1:RRN1025. doi:10.1371/currents.RRN1025. PMID:20029611.
   PubMedGoogle Scholar
• Nassim C, Christensen S, Henry D, Holmes S, Hohenboken M, Kanesa-Thasan N. Identification of antigen and adjuvant doses resulting in optimal immunogenicity and antibody persistence up to 1 year after immunization with a pandemic A/H1N1 influenza vaccine in children 3 to < 9 years of age. Pediatr Infect Dis J. 2012;31:e59–65. doi:10.1097/INF.0b013e31824b9545. PMID:22418661.
   PubMed Web of Science ®Google Scholar
• Atmar RL, Keitel WA, Patel SM, Katz JM, She D, El Sahly H, et al. Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations. Clin Infect Dis. 2006;43:1135–42. doi:10.1086/508174. PMID:17029131.
   PubMed Web of Science ®Google Scholar
• Langley JM, Frenette L, Jeanfreau R, Halperin SA, Kyle M, Chu L, et al. Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: a randomized controlled clinical trial. Vaccine. 2015;33:559–67. doi:10.1016/j.vaccine.2014.11.018. PMID:25448092.
   PubMed Web of Science ®Google Scholar
• Vajo Z, Balaton G, Vajo P, Kalabay L, Erdman A, Torzsa P. Dose sparing and the lack of a dose–response relationship with an influenza vaccine in adult and elderly patients – a randomized, double-blind clinical trial. Br J Clin Pharmacol. 2017;83:1912–20. doi:10.1111/bcp.13289. PMID:28378403.
   PubMed Web of Science ®Google Scholar
• Gordon DL, Sajkov D, Honda-Okubo Y, Wilks SH, Aban M, Barr IG, et al. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant. Vaccine. 2016;34:3780–6. doi:10.1016/j.vaccine.2016.05.071. PMID:27342914.
   PubMed Web of Science ®Google Scholar
• Fischetti L, Zhong Z, Pinder CL, Tregoning JS, Shattock RJ. The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling. Cytokine. 2017;99:287–296. doi:10.1016/j.cyto.2017.08.009. PMID:28826648.
   PubMed Web of Science ®Google Scholar
• Knudsen NP, Olsen A, Buonsanti C, Follmann F, Zhang Y, Coler RN, et al. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens. Sci Rep. 2016;6:19570. doi:10.1038/srep19570. PMID:26791076.
   PubMed Web of Science ®Google Scholar
• Gluck U, Gebbers JO, Gluck R. Phase 1 evaluation of intranasal virosomal influenza vaccine with and without Escherichia coli heat-labile toxin in adult volunteers. J Virol. 1999;73:7780–6. PMID:10438868.
   PubMed Web of Science ®Google Scholar
• Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013;4:114. doi:10.3389/fimmu.2013.00114. PMID:23720661.
   PubMed Web of Science ®Google Scholar
• Hutchison S, Benson RA, Gibson VB, Pollock AH, Garside P, Brewer JM. Antigen depot is not required for alum adjuvanticity. FASEB J. 2012;26:1272–9. doi:10.1096/fj.11-184556. PMID:22106367.
   PubMed Web of Science ®Google Scholar
• Mosca F, Tritto E, Muzzi A, Monaci E, Bagnoli F, Iavarone C, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci U S A 2008;105:10501–6. doi:10.1073/pnas.0804699105. PMID:18650390.
   PubMed Web of Science ®Google Scholar
• Bobanga ID, Petrosiute A, Huang AY. Chemokines as cancer vaccine Adjuvants. Vaccines. 2013;1:444–62. doi:10.3390/vaccines1040444. PMID:24967094.
   PubMedGoogle Scholar
• Goto N, Akama K. Histopathological studies of reactions in mice injected with aluminum-adsorbed tetanus toxoid. Microbiol Immunol. 1982;26:1121–32. doi:10.1111/j.1348-0421.1982.tb00261.x. PMID:7169970.
   PubMed Web of Science ®Google Scholar
• Morefield GL, Sokolovska A, Jiang D, HogenEsch H, Robinson JP, Hem SL. Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro. Vaccine. 2005;23:1588–95. doi:10.1016/j.vaccine.2004.07.050. PMID:15694511.
   PubMed Web of Science ®Google Scholar
• Calabro S, Tortoli M, Baudner BC, Pacitto A, Cortese M, O'Hagan DT, et al. Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine. 2011;29:1812–23. doi:10.1016/j.vaccine.2010.12.090. PMID:21215831.
   PubMed Web of Science ®Google Scholar
• Coyle AJ, Gutierrez-Ramos JC. The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T cell function. Nat Immunol. 2001;2:203–9. doi:10.1038/85251. PMID:11224518.
   PubMed Web of Science ®Google Scholar
• Seubert A, Monaci E, Pizza M, O'Hagan DT, Wack A. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol. 2008;180:5402–12. doi:10.4049/jimmunol.180.8.5402. PMID:18390722.
   PubMed Web of Science ®Google Scholar
• Taylor DN, Treanor JJ, Sheldon EA, Johnson C, Umlauf S, Song L, et al. Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Vaccine. 2012;30:5761–9. doi:10.1016/j.vaccine.2012.06.086. PMID:22796139.
   PubMed Web of Science ®Google Scholar
• Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453:1122–6. doi:10.1038/nature06939. PMID:18496530.
   PubMed Web of Science ®Google Scholar
• Pasare C, Medzhitov R. Control of B-cell responses by Toll-like receptors. Nature (London). 2005;438:364–8. doi:10.1038/nature04267.
   PubMed Web of Science ®Google Scholar
• Mastelic Gavillet B, Eberhardt CS, Auderset F, Castellino F, Seubert A, Tregoning JS, et al. MF59 mediates its B cell adjuvanticity by promoting T follicular helper cells and thus germinal center responses in adult and early life. J Immunol. 2015;194:4836–45. doi:10.4049/jimmunol.1402071.
   PubMed Web of Science ®Google Scholar
• Spreafico R, Ricciardi-Castagnoli P, Mortellaro A. The controversial relationship between NLRP3, alum, danger signals and the next-generation adjuvants. Eur J Immunol 2010;40:638–42. doi:10.1002/eji.200940039. PMID:20201020.
   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;9:287–93. doi:10.1038/nri2510. PMID:19247370.
   PubMed Web of Science ®Google Scholar
• Ghimire TR. The mechanisms of action of vaccines containing aluminum adjuvants: an in vitro vs in vivo paradigm. Springer Plus. 2015;4:181. doi:10.1186/s40064-015-0972-0. PMID:25932368.
   PubMed Web of Science ®Google Scholar
• Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, et al. Cutting edge: Alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol. 2008;181:3755–9. doi:10.4049/jimmunol.181.6.3755.
   PubMed Web of Science ®Google Scholar
• Chioato A, Noseda E, Felix SD, Stevens M, Del Giudice G, Fitoussi S, et al. Influenza and meningococcal vaccinations are effective in healthy subjects treated with the interleukin-1β-blocking antibody canakinumab: Results of an open-label, parallel group, randomized, single-center study. Clin Vaccine Immunol. 2010;17:1952–7. doi:10.1128/CVI.00175-10. PMID:20962212.
   PubMed Web of Science ®Google Scholar
• McKee AS, Burchill MA, Munks MW, Jin L, Kappler JW, Friedman RS, et al. Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells. Proc Natl Acad Sci U S A. 2013;110:E1122–31. doi:10.1073/pnas.1300392110. PMID:23447566.
   PubMed Web of Science ®Google Scholar
• Lu F, Hogenesch H. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant. Vaccine. 2013;31:3979–86. doi:10.1016/j.vaccine.2013.05.107. PMID:23770306.
   PubMed Web of Science ®Google Scholar
• Ghimire TR, Benson RA, Garside P, Brewer JM. Alum increases antigen uptake, reduces antigen degradation and sustains antigen presentation by DCs in vitro. Immunol Lett. 2012;147:55–62. doi:10.1016/j.imlet.2012.06.002. PMID:22732235.
   PubMed Web of Science ®Google Scholar
• Sokolovska A, Hem SL, HogenEsch H. Activation of dendritic cells and induction of CD4(+) T cell differentiation by aluminum-containing adjuvants. Vaccine. 2007;25:4575–85. doi:10.1016/j.vaccine.2007.03.045. PMID:17485153.
   PubMed Web of Science ®Google Scholar
• O'Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD. The history of MF59((R)) adjuvant: A phoenix that arose from the ashes. Expert Rev Vaccines. 2013;12:13–30. doi:10.1586/erv.12.140. PMID:23256736.
   PubMed Web of Science ®Google Scholar
• Salk JE, Laurent AM, Bailey ML. Direction of research on vaccination against influenza;new studies with immunologic adjuvants. Am J Public Health Nations Health. 1951;41:669–77. doi:10.2105/AJPH.41.6.669. PMID:14838187.
   PubMed Web of Science ®Google Scholar
• Edelman R. Vaccine adjuvants. Rev Infect Dis. 1980;2:370–83. doi:10.1093/clinids/2.3.370. PMID:6997966.
   PubMedGoogle Scholar
• O'Hagan DT, Ott GS, De Gregorio E, Seubert A. The mechanism of action of MF59 – an innately attractive adjuvant formulation. Vaccine. 2012;30:4341–8. doi:10.1016/j.vaccine.2011.09.061. PMID:22682289.
   PubMed Web of Science ®Google Scholar
• Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G. MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol. 1995;6:277–96. doi:10.1007/978-1-4615-1823-5_10. PMID:7551221.
   PubMedGoogle Scholar
• Seubert A, Calabro S, Santini L, Galli B, Genovese A, Valentini S, et al. Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88. Proc Natl Acad Sci U S A. 2011;108:11169–74. doi:10.1073/pnas.1107941108. PMID:21690334.
   PubMed Web of Science ®Google Scholar
• Ellebedy AH, Lupfer C, Ghoneim HE, DeBeauchamp J, Kanneganti TD, Webby RJ. Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59. Proc Natl Acad Sci U S A. 2011;108:2927–32. doi:10.1073/pnas.1012455108. PMID:21270336.
   PubMed Web of Science ®Google Scholar
• McDonald JU, Zhong Z, Groves HT, Tregoning JS. Inflammatory responses to influenza vaccination at the extremes of age. Immunology. 2017;151:451–63. doi:10.1111/imm.12742. PMID:28375554.
   PubMed Web of Science ®Google Scholar
• Calabro S, Tritto E, Pezzotti A, Taccone M, Muzzi A, Bertholet S, et al. The adjuvant effect of MF59 is due to the oil-in-water emulsion formulation, none of the individual components induce a comparable adjuvant effect. Vaccine. 2013;31:3363–9. doi:10.1016/j.vaccine.2013.05.007. PMID:23684834.
   PubMed Web of Science ®Google Scholar
• Dupuis M, McDonald DM, Ott G. Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection in mice. Vaccine. 1999;18:434–9. doi:10.1016/S0264-410X(99)00263-7. PMID:10519932.
   PubMed Web of Science ®Google Scholar
• Garcon N, Di Pasquale A. From discovery to licensure, the Adjuvant System story. Human Vaccines & Immunotherapeutics. 2017;13:19–33. doi:10.1080/21645515.2016.1225635.
   PubMed Web of Science ®Google Scholar
• Morel S, Didierlaurent A, Bourguignon P, Delhaye S, Baras B, Jacob V, et al. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine. 2011;29:2461–73. doi:10.1016/j.vaccine.2011.01.011. PMID:21256188.
   PubMed Web of Science ®Google Scholar
• Garcon N, Vaughn DW, Didierlaurent AM. Development and evaluation of AS03, an Adjuvant System containing alpha-tocopherol and squalene in an oil-in-water emulsion. Expert Rev Vaccines. 2012;11:349–66. doi:10.1586/erv.11.192. PMID:22380826.
   PubMed Web of Science ®Google Scholar
• Burny W, Callegaro A, Bechtold V, Clement F, Delhaye S, Fissette L, 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. PMID:28144241.
   PubMed Web of Science ®Google Scholar
• Moris P, van der Most R, Leroux-Roels I, Clement F, Dramé M, Hanon E, et al. H5N1 influenza vaccine formulated with AS03(A) induces strong cross-Reactive and polyfunctional CD4 T-cell responses. J Clin Immunol. 2011;31:443–54. doi:10.1007/s10875-010-9490-6. PMID:21174144.
   PubMed Web of Science ®Google Scholar
• Klucker MF, Dalençon F, Probeck P, Haensler J. AF03, an alternative squalene emulsion‐based vaccine adjuvant prepared by a phase inversion temperature method. J Pharm Sci. 2012;101:4490–500. doi:10.1002/jps.23311. PMID:22941944.
   PubMed Web of Science ®Google Scholar
• Moser C, Müller M, Kaeser MD, Weydemann U, Amacker M. Influenza virosomes as vaccine adjuvant and carrier system. Expert Review of Vaccines. 2013;12:779–91. doi:10.1586/14760584.2013.811195. PMID:23885823.
   PubMed Web of Science ®Google Scholar
• Bachmann MF, Jennings GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010;10:787–96. doi:10.1038/nri2868. PMID:20948547.
   PubMed Web of Science ®Google Scholar
• Kanra G, Marchisio P, Feiterna-Sperling C, Gaedicke G, Lazar H, Durrer P, et al. Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children. Pediatr Infect Dis J. 2004;23:300–6. doi:10.1097/00006454-200404000-00005. PMID:15071282.
   PubMed Web of Science ®Google Scholar
• Vesikari T, Forsten A, Arora A, Tsai T, Clemens R. Influenza vaccination in children primed with MF59-adjuvanted or non-adjuvanted seasonal influenza vaccine. Hum Vaccin Immunother 2015;11:2102–12. doi:10.1080/21645515.2015.1044167. PMID:26091244.
   PubMed Web of Science ®Google Scholar
• Zedda L, Forleo-Neto E, Vertruyen A, Raes M, Marchant A, Jansen W, et al. Dissecting the immune response to MF59-adjuvanted and nonadjuvanted seasonal influenza vaccines in children less than three years of age. Pediatr Infect Dis J. 2015;34:73–8. doi:10.1097/INF.0000000000000465. PMID:25037034.
   PubMed Web of Science ®Google Scholar
• Belshe RB, Frey SE, Graham IL, Anderson EL, Jackson LA, Spearman P, et al. Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: A randomized clinical trial. JAMA. 2014;312:1420–8. doi:10.1001/jama.2014.12609. PMID:25291578.
   PubMed Web of Science ®Google Scholar
• Vesikari T, Pepin S, Kusters I, Hoffenbach A, Denis M. Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age. Hum Vaccin Immunother. 2012;8:1283–92. doi:10.4161/hv.21265. PMID:22906943.
   PubMed Web of Science ®Google Scholar
• Moris P, van der Most R, Leroux-Roels I, Clement F, Drame M, Hanon E, et al. H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol. 2011;31:443–54. doi:10.1007/s10875-010-9490-6. PMID:21174144.
   PubMed Web of Science ®Google Scholar
• Domnich A, Arata L, Amicizia D, Puig-Barberà J, Gasparini R, Panatto D. Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis. Vaccine. 2017;35:513–20. doi:10.1016/j.vaccine.2016.12.011. PMID:28024956.
   PubMed Web of Science ®Google Scholar
• Jackson LA, Campbell JD, Frey SE, Edwards KM, Keitel WA, Kotloff KL, et al. Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response: A Randomized Clinical Trial. JAMA. 2015;314:237–46. doi:10.1001/jama.2015.7916. PMID:26197184.
   PubMed Web of Science ®Google Scholar
• Banzhoff A, Nacci P, Podda A. A new MF59-adjuvanted influenza vaccine enhances the immune response in the elderly with chronic diseases: results from an immunogenicity meta-analysis. Gerontology. 2003;49:177–84. doi:10.1159/000069172. PMID:12679609.
   PubMed Web of Science ®Google Scholar
• Rumke HC, Bayas JM, de Juanes JR, Caso C, Richardus JH, Campins M, et al. Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial. Vaccine. 2008;26:2378–88. doi:10.1016/j.vaccine.2008.02.068. PMID:18407382.
   PubMed Web of Science ®Google Scholar
• Langley JM, Risi G, Caldwell M, Gilderman L, Berwald B, Fogarty C, et al. Dose-sparing H5N1 A/Indonesia/05/2005 pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-controlled, randomized study. J Infect Dis. 2011;203:1729–38. doi:10.1093/infdis/jir172. PMID:21606531.
   PubMed Web of Science ®Google Scholar
• Diez-Domingo J, Baldo JM, Planelles-Catarino MV, Garces-Sanchez M, Ubeda I, Jubert-Rosich A, et al. Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination. Influenza Other Respir Viruses. 2015;9:68–77. doi:10.1111/irv.12295. PMID:25652873.
   PubMed Web of Science ®Google Scholar
• Ikematsu H, Tenjinbaru K, Li P, Madan A, Vaughn D. Evaluation of immune response following one dose of an AS03A-adjuvanted H1N1 2009 pandemic influenza vaccine in Japanese adults 65 years of age or older. Hum Vaccin Immunother. 2012;8:1119–25. doi:10.4161/hv.21081. PMID:22854661.
   PubMed Web of Science ®Google Scholar
• Roman F, Vaman T, Gerlach B, Markendorf A, Gillard P, Devaster JM. Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant: Preliminary report of an observer-blind, randomised trial. Vaccine. 2010;28:1740–5. doi:10.1016/j.vaccine.2009.12.014. PMID:20034605.
   PubMed Web of Science ®Google Scholar
• Roman F, Vaman T, Kafeja F, Hanon E, Van Damme P. AS03(A)-Adjuvanted influenza A (H1N1) 2009 vaccine for adults up to 85 years of age. Clin Infect Dis. 2010;51:668–77. doi:10.1086/655830. PMID:20687838.
   PubMed Web of Science ®Google Scholar
• Carmona A, Omenaca F, Tejedor JC, Merino JM, Vaman T, Dieussaert I, et al. Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6–35 months. Vaccine. 2010;28:5837–44. doi:10.1016/j.vaccine.2010.06.065. PMID:20600478.
   PubMed Web of Science ®Google Scholar
• Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine. 2001;19:2673–80. doi:10.1016/S0264-410X(00)00499-0. PMID:11257408.
   PubMed Web of Science ®Google Scholar
• Giezeman KM, Nauta J, de Bruijn IA, Palache AM. Trivalent inactivated subunit influenza vaccine Influvac: 25-Year experience of safety and immunogenicity. Vaccine. 2009;27:2414–7. doi:10.1016/j.vaccine.2009.02.008. PMID:19368782.
   PubMed Web of Science ®Google Scholar
• Herzog C, Hartmann K, Kunzi V, Kursteiner O, Mischler R, Lazar H, et al. Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine. 2009;27:4381–7. doi:10.1016/j.vaccine.2009.05.029. PMID:19450630.
   PubMed Web of Science ®Google Scholar
• Nohynek H, Jokinen J, Partinen M, Vaarala O, Kirjavainen T, Sundman J, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PloS one. 2012;7:e33536. doi:10.1371/journal.pone.0033536. PMID:22470453.
   PubMed Web of Science ®Google Scholar
• Miller E, Andrews N, Stellitano L, Stowe J, Winstone AM, Shneerson J, et al. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. Bmj. 2013;346:f794. doi:10.1136/bmj.f794. PMID:23444425.
   PubMed Web of Science ®Google Scholar
• Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med. 2015;7:294ra105. doi:10.1126/scitranslmed.aab2354. PMID:26136476.
   PubMed Web of Science ®Google Scholar
• Ahmed SS, Steinman L. Mechanistic insights into influenza vaccine-associated narcolepsy. Human Vaccines & Immunotherapeutics. 2016;12:3196–201. doi:10.1080/21645515.2016.1171439.
   PubMed Web of Science ®Google Scholar
• Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, et al. Use of the inactivated intranasal influenza vaccine and the risk of bell's palsy in switzerland. N Engl J Med. 2004;350:896–903. doi:10.1056/NEJMoa030595. PMID:14985487.
   PubMed Web of Science ®Google Scholar
• Lewis DJ, Huo Z, Barnett S, Kromann I, Giemza R, Galiza E, et al. Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PloS one. 2009;4:e6999. doi:10.1371/journal.pone.0006999. PMID:19756141.
   PubMed Web of Science ®Google Scholar
• Okado N, Hayashi H, Hosoya Y, Matsukawa M. Retrograde neuronal labelling by E. coli enterotoxin subunit B. Neurosci Lett. 1990;120:263–6. doi:10.1016/0304-3940(90)90055-E. PMID:1705684.
   PubMed Web of Science ®Google Scholar
• van Ginkel FW, Jackson RJ, Yuki Y, McGhee JR. Cutting Edge: The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. Eur J Immunol. 2000;165:4778–82. doi:10.4049/jimmunol.165.9.4778. PMID:11045998.
   PubMedGoogle Scholar
• Weibel RE, Woodhour AF, Stokes J, Jr., Metzgar DP, Hilleman MR. New metabolizable immunologic adjuvant for human use. 5. Evaluation of highly purified influenza-virus vaccine in adjuvant 65. N Engl J Med. 1967;276:78–84. doi:10.1056/NEJM196701122760203. PMID:6015520.
   PubMed Web of Science ®Google Scholar
• De Gregorio E. The path forward. Vaccine. 2015;33 Suppl 2:B60–3. doi:10.1016/j.vaccine.2015.01.087. PMID:26022572.
   PubMedGoogle Scholar
• Hennessy EJ, Parker AE, O'Neill LA. Targeting Toll-like receptors: emerging therapeutics? Nature Reviews Drug Discovery. 2010;9:293–307. doi:10.1038/nrd3203. PMID:20380038.
   PubMed Web of Science ®Google Scholar
• van den Ancker W, van Luijn MM, Ruben JM, Westers TM, Bontkes HJ, Ossenkoppele GJ, et al. Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation. Cancer Immunol Immunother: CII. 2011;60:37–47. doi:10.1007/s00262-010-0917-y. PMID:20859626.
   PubMed Web of Science ®Google Scholar
• Treanor JJ, Essink B, Hull S, Reed S, Izikson R, Patriarca P, et al. Evaluation of safety and immunogenicity of recombinant influenza hemagglutinin (H5/Indonesia/05/2005) formulated with and without a stable oil-in-water emulsion containing glucopyranosyl-lipid A (SE+GLA) adjuvant. Vaccine. 2013;31:5760–5. doi:10.1016/j.vaccine.2013.08.064. PMID:24075920.
   PubMed Web of Science ®Google Scholar
• Hung IF, Zhang AJ, To KK, Chan JF, Li P, Wong TL, et al. Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial. Lancet Infect Dis. 2016;16:209–18. doi:10.1016/S1473-3099(15)00354-0. PMID:26559482.
   PubMed Web of Science ®Google Scholar
• Overton ET, Goepfert PA, Cunningham P, Carter WA, Horvath J, Young D, et al. Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans. Vaccine. 2014;32:5490–5. doi:10.1016/j.vaccine.2014.07.078. PMID:25128802.
   PubMed Web of Science ®Google Scholar
• Cooper CL, Davis HL, Morris ML, Efler SM, Krieg AM, Li Y, et al. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine. 2004;22:3136–43. doi:10.1016/j.vaccine.2004.01.058. PMID:15297066.
   PubMed Web of Science ®Google Scholar
• Turley CB, Rupp RE, Johnson C, Taylor DN, Wolfson J, Tussey L, et al. Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine. 2011;29:5145–52. doi:10.1016/j.vaccine.2011.05.041. PMID:21624416.
   PubMed Web of Science ®Google Scholar
• Ben-Yehuda A, Joseph A, Barenholz Y, Zeira E, Even-Chen S, Louria-Hayon I, et al. Immunogenicity and safety of a novel IL-2-supplemented liposomal influenza vaccine (INFLUSOME-VAC) in nursing-home residents. Vaccine. 2003;21:3169–78. doi:10.1016/S0264-410X(03)00251-2. PMID:12804845.
   PubMed Web of Science ®Google Scholar
• Somani J, Lonial S, Rosenthal H, Resnick S, Kakhniashvili I, Waller EK. A randomized, placebo-controlled trial of subcutaneous administration of GM-CSF as a vaccine adjuvant: effect on cellular and humoral immune responses. Vaccine. 2002;21:221–30. doi:10.1016/S0264-410X(02)00463-2. PMID:12450697.
   PubMed Web of Science ®Google Scholar
• Couch RB, Atmar RL, Cate TR, Quarles JM, Keitel WA, Arden NH, et al. Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans. Vaccine. 2009;27:5344–8. doi:10.1016/j.vaccine.2009.06.084. PMID:19607949.
   PubMed Web of Science ®Google Scholar
• Tregoning JS, Kinnear E. Using Plasmids as DNA Vaccines for Infectious Diseases. Microbiol Spectr. 2014;2(6). doi:10.1128/microbiolspec.PLAS-0028-2014. PMID:26104452.
   PubMedGoogle Scholar
• Kalams SA, Parker SD, Elizaga M, Metch B, Edupuganti S, Hural J, et al. Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis. 2013;208:818–29. doi:10.1093/infdis/jit236. PMID:23840043.
   PubMed Web of Science ®Google Scholar
• Perales M-A, Yuan J, Powel S, Gallardo HF, Rasalan TS, Gonzalez C, et al. Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma. Mol Ther: J Am Soc Gene Therapy. 2008;16:2022–9. doi:10.1038/mt.2008.196. PMID:18797450.
   PubMed Web of Science ®Google Scholar
• Garcon N, Chomez P, Van Mechelen M. GlaxoSmithKline adjuvant systems in vaccines: Concepts, achievements and perspectives. Expert review of vaccines. 2007;6:723–39. doi:10.1586/14760584.6.5.723. PMID:17931153.
   PubMed Web of Science ®Google Scholar
• Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, et al. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011;365:1863–75. doi:10.1056/NEJMoa1102287. PMID:22007715.
   PubMed Web of Science ®Google Scholar
• Rts SCTP, Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, et al. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012;367:2284–95. doi:10.1056/NEJMoa1208394. PMID:23136909.
   PubMed Web of Science ®Google Scholar
• Tong NK, Beran J, Kee SA, Miguel JL, Sanchez C, Bayas JM, et al. Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int. 2005;68:2298–303. doi:10.1111/j.1523-1755.2005.00689.x. PMID:16221232.
   PubMed Web of Science ®Google Scholar
• Wiersma LCM, Rimmelzwaan GF, de Vries RD. Developing universal influenza vaccines: Hitting the nail, not just on the head. Vaccines. 2015;3:239–62. doi:10.3390/vaccines3020239. PMID:26343187.
   PubMed Web of Science ®Google Scholar
• Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem. 2000;69:531–69. doi:10.1146/annurev.biochem.69.1.531. PMID:10966468.
   PubMed Web of Science ®Google Scholar
• Ekiert DC, Bhabha G, Elsliger M-A, Friesen RHE, Jongeneelen M, Throsby M, et al. Antibody recognition of a highly conserved influenza virus epitope: Implications for universal prevention and therapy. Science (New York, NY). 2009;324:246–51. doi:10.1126/science.1171491.
   Google Scholar
• Korsholm KS, Hansen J, Karlsen K, Filskov J, Mikkelsen M, Lindenstrom T, et al. Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant. Vaccine. 2014;32:3927–35. doi:10.1016/j.vaccine.2014.05.050. PMID:24877765.
   PubMed Web of Science ®Google Scholar
• Riedl K, Riedl R, von Gabain A, Nagy E, Lingnau K. The novel adjuvant IC31 strongly improves influenza vaccine-specific cellular and humoral immune responses in young adult and aged mice. Vaccine. 2008;26:3461–8. doi:10.1016/j.vaccine.2008.04.029. PMID:18495302.
   PubMed Web of Science ®Google Scholar
• Sridhar S. Heterosubtypic T-Cell immunity to influenza in humans: Challenges for universal T-Cell Influenza vaccines. Front Immunol. 2016;7:195. doi:10.3389/fimmu.2016.00195. PMID:27242800.
   PubMed Web of Science ®Google Scholar
• Gilbert SC. T-cell-inducing vaccines – what's the future. Immunology. 2012;135:19–26. doi:10.1111/j.1365-2567.2011.03517.x. PMID:22044118.
   PubMed Web of Science ®Google Scholar
• Townsend ARM, Skehel JJ. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med. 1984;160:552–63. doi:10.1084/jem.160.2.552. PMID:6206181.
   PubMed Web of Science ®Google Scholar
• McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983;309:13–7. doi:10.1056/NEJM198307073090103. PMID:6602294.
   PubMed Web of Science ®Google Scholar
• Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19:1305–12. doi:10.1038/nm.3350. PMID:24056771.
   PubMed Web of Science ®Google Scholar
• Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18:274–80. doi:10.1038/nm.2612. PMID:22286307.
   PubMed Web of Science ®Google Scholar
• Gould VMW, Francis JN, Anderson KJ, Georges B, Cope AV, Tregoning JS. Nasal igA provides protection against human influenza challenge in volunteers with low serum influenza antibody titre. Front Microbiol. 2017;8:900. doi:10.3389/fmicb.2017.00900. PMID:28567036.
   PubMed Web of Science ®Google Scholar
• Kinnear E, Lambert L, McDonald JU, Cheeseman HM, Caproni LJ, Tregoning JS. Airway T cells protect against RSV infection in the absence of antibody. Mucosal Immunol. 2018;11(1):249–256. doi:10.1038/mi.2017.79.
   PubMed Web of Science ®Google Scholar
• Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, et al. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nature Commun. 2015;6:10224. doi:10.1038/ncomms10224. PMID:26687547.
   PubMed Web of Science ®Google Scholar
• Falloon J, Talbot K, Curtis C, Ervin J, Krieger D, Dubovsky F, et al. Dose selection for an adjuvanted respiratory syncytial virus F protein vaccine for older adults based on humoral and cellular immune responses. Clin Vaccine Immunol. 2017;24(9). pii:e00157–17. doi:10.1128/CVI.00157-17. PMID:28679495.
   PubMed Web of Science ®Google Scholar
• Falloon J, Ji F, Curtis C, Bart S, Sheldon E, Krieger D, et al. A phase 1a, first-in-human, randomized study of a respiratory syncytial virus F protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant. Vaccine. 2016;34:2847–54. doi:10.1016/j.vaccine.2016.04.002. PMID:27102821.
   PubMed Web of Science ®Google Scholar
• Barbosa A, Naniche D, Aponte JJ, Manaca MN, Mandomando I, Aide P, et al. Plasmodium falciparum-specific cellular immune responses after immunization with the RTS,S/AS02D candidate malaria vaccine in infants living in an area of high endemicity in Mozambique. Infect Immun. 2009;77:4502–9. doi:10.1128/IAI.00442-09. PMID:19651872.
   PubMed Web of Science ®Google Scholar
• Dormitzer PR, Grandi G, Rappuoli R. Structural vaccinology starts to deliver. Nat Rev Micro. 2012;10:807–13. doi:10.1038/nrmicro2893.
   PubMed Web of Science ®Google Scholar
• Henry C, Palm A-KE, Krammer F, Wilson PC. From original antigenic sin to the universal influenza virus vaccine. Trends Immunol. 2018;39(1):70–79. doi:10.1016/j.it.2017.08.003. PMID:28867526.
   PubMed Web of Science ®Google Scholar
• Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. 2014;5:446. doi:10.3389/fimmu.2014.00446. PMID:25278941.
   PubMed Web of Science ®Google Scholar
• Costa-Carvalho BT, Vieria HM, Dimantas RB, Arslanian C, Naspitz CK, Sole D, et al. Transfer of IgG subclasses across placenta in term and preterm newborns. Braz J Med Biol Res. 1996;29:201–4. PMID:8731349.
   PubMed Web of Science ®Google Scholar
• Cox RJ, Major D, Pedersen G, Pathirana RD, Hoschler K, Guilfoyle K, et al. Matrix M H5N1 vaccine induces cross-H5 clade humoral immune responses in a randomized clinical trial and provides protection from highly pathogenic influenza challenge in ferrets. PloS one. 2015;10:e0131652. doi:10.1371/journal.pone.0131652. PMID:26147369.
   PubMed Web of Science ®Google Scholar
• Atsmon J, Kate-Ilovitz E, Shaikevich D, Singer Y, Volokhov I, Haim KY, et al. Safety and Immunogenicity of Multimeric-001—a Novel Universal Influenza Vaccine. J Clin Immunol. 2012;32:595–603. doi:10.1007/s10875-011-9632-5. PMID:22318394.
   PubMed Web of Science ®Google Scholar
• Lambkin-Williams R, Gelder C, Broughton R, Mallett CP, Gilbert AS, Mann A, et al. An intranasal proteosome-adjuvanted trivalent influenza vaccine is safe, immunogenic & efficacious in the human viral influenza challenge model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection. PloS one. 2016;11:e0163089. doi:10.1371/journal.pone.0163089. PMID:28005959.
   PubMed Web of Science ®Google Scholar
• Stanberry LR, Simon JK, Johnson C, Robinson PL, Morry J, Flack MR, et al. Safety and immunogenicity of a novel nanoemulsion mucosal adjuvant W805EC combined with approved seasonal influenza antigens. Vaccine. 2012;30:307–16. doi:10.1016/j.vaccine.2011.10.094. PMID:22079079.
   PubMed Web of Science ®Google Scholar
• Rimmelzwaan GF, Nieuwkoop N, Brandenburg A, Sutter G, Beyer WE, Maher D, et al. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Vaccine. 2000;19:1180–7. doi:10.1016/S0264-410X(00)00310-8. PMID:11137255.
   PubMed Web of Science ®Google Scholar
• Powers DC, Manning MC, Hanscome PJ, Pietrobon PJ. Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus vaccine in the elderly. J Infect Dis. 1995;172:1103–7. doi:10.1093/infdis/172.4.1103. PMID:7561189.
   PubMed Web of Science ®Google Scholar
• Glenn GM, Thomas DN, Poffenberger KL, Flyer DC, Ellingsworth LR, Andersen BH, et al. Safety and immunogenicity of an influenza vaccine A/H5N1 (A/Vietnam/1194/2004) when coadministered with a heat-labile enterotoxin (LT) adjuvant patch. Vaccine. 2009;27 Suppl 6:G60–6. doi:10.1016/j.vaccine.2009.10.031. PMID:20006142.
   PubMedGoogle Scholar
• Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA, van Crevel R, et al. BCG Vaccination enhances the immunogenicity of subsequent influenza vaccination in healthy volunteers: A randomized, placebo-controlled pilot study. J Infect Dis. 2015;212:1930–8. doi:10.1093/infdis/jiv332. PMID:26071565.
   PubMed Web of Science ®Google Scholar
• Li L, Honda-Okubo Y, Li C, Sajkov D, Petrovsky N. Delta inulin adjuvant enhances plasmablast generation, expression of activation-induced cytidine deaminase and B-Cell affinity maturation in human subjects receiving seasonal influenza vaccine. PloS one. 2015;10:e0132003. doi:10.1371/journal.pone.0132003. PMID:26177480.
   PubMed Web of Science ®Google Scholar
• Gordon DL, Sajkov D, Woodman RJ, Honda-Okubo Y, Cox MM, Heinzel S, et al. Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax polysaccharide adjuvant. Vaccine. 2012;30:5407–16. doi:10.1016/j.vaccine.2012.06.009. PMID:23840043.
   PubMed Web of Science ®Google Scholar
• Esposito S, Marchisio P, Prada E, Daleno C, Porretti L, Carsetti R, et al. Impact of a mixed bacterial lysate (OM-85 BV) on the immunogenicity, safety and tolerability of inactivated influenza vaccine in children with recurrent respiratory tract infection. Vaccine. 2014;32:2546–52. doi:10.1016/j.vaccine.2014.03.055. PMID:24681270.
   PubMed Web of Science ®Google Scholar
• Langley JM, Aoki F, Ward BJ, McGeer A, Angel JB, Stiver G, et al. A nasally administered trivalent inactivated influenza vaccine is well tolerated, stimulates both mucosal and systemic immunity, and potentially protects against influenza illness. Vaccine. 2011;29:1921–8. doi:10.1016/j.vaccine.2010.12.100. PMID:21219987.
   PubMed Web of Science ®Google Scholar
• Brignone C, Grygar C, Marcu M, Perrin G, Triebel F. IMP321 (sLAG-3) safety and T cell response potentiation using an influenza vaccine as a model antigen: A single-blind phase I study. Vaccine. 2007;25:4641–50. doi:10.1016/j.vaccine.2007.04.019. PMID:17493710.
   PubMed Web of Science ®Google Scholar
• Mbawuike I, Zang Y, Couch RB. Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant. Vaccine. 2007;25:3263–9. doi:10.1016/j.vaccine.2007.01.073. PMID:17280748.
   PubMed Web of Science ®Google Scholar
• Evans TG, Judd ME, Dowell T, Poe S, Daynes RA, Araneo BA. The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and influenza vaccination of the elderly. Vaccine. 1996;14:1531–7. doi:10.1016/S0264-410X(96)00095-3. PMID:9014295.
   PubMed Web of Science ®Google Scholar
• Degelau J, Guay D, Hallgren H. The effect of DHEAS on influenza vaccination in aging adults. J Am Geriatr Soc. 1997;45:747–51. doi:10.1111/j.1532-5415.1997.tb01482.x. PMID:9180672.
   PubMed Web of Science ®Google Scholar