Matrix M^TM adjuvanted virosomal H5N1 vaccine induces balanced Th1/Th2 CD4⁺ T cell responses in man

References

• Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G, Hanson A, Katsura H, Watanabe S, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012; 486:420 - 8; PMID: 22722205
   PubMed Web of Science ®Google Scholar
• Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012; 336:1534 - 41; http://dx.doi.org/10.1126/science.1213362; PMID: 22723413
   PubMed Web of Science ®Google Scholar
• Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:36 - 44; http://dx.doi.org/10.1016/S1473-3099(11)70295-X; PMID: 22032844
   PubMed Web of Science ®Google Scholar
• Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2010; CD001269; PMID: 20614424
   PubMed Web of Science ®Google Scholar
• McKinstry KK, Strutt TM, Swain SL. The potential of CD4 T-cell memory. Immunology 2010; 130:1 - 9; http://dx.doi.org/10.1111/j.1365-2567.2010.03259.x; PMID: 20331470
   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; http://dx.doi.org/10.1056/NEJM198307073090103; PMID: 6602294
   PubMed Web of Science ®Google Scholar
• Stambas J, Guillonneau C, Kedzierska K, Mintern JD, Doherty PC, La Gruta NL. Killer T cells in influenza. Pharmacol Ther 2008; 120:186 - 96; http://dx.doi.org/10.1016/j.pharmthera.2008.08.007; PMID: 18801385
   PubMed Web of Science ®Google Scholar
• Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med 2012; 18:274 - 80; http://dx.doi.org/10.1038/nm.2612; PMID: 22286307
   PubMed Web of Science ®Google Scholar
• Moran TM, Park H, Fernandez-Sesma A, Schulman JL. Th2 responses to inactivated influenza virus can Be converted to Th1 responses and facilitate recovery from heterosubtypic virus infection. J Infect Dis 1999; 180:579 - 85; http://dx.doi.org/10.1086/314952; PMID: 10438342
   PubMed Web of Science ®Google Scholar
• Graham MB, Braciale VL, Braciale TJ. Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J Exp Med 1994; 180:1273 - 82; http://dx.doi.org/10.1084/jem.180.4.1273; PMID: 7931062
   PubMed Web of Science ®Google Scholar
• Duvall MG, Precopio ML, Ambrozak DA, Jaye A, McMichael AJ, Whittle HC, Roederer M, Rowland-Jones SL, Koup RA. Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol 2008; 38:350 - 63; http://dx.doi.org/10.1002/eji.200737768; PMID: 18200635
   PubMed Web of Science ®Google Scholar
• Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 2007; 13:843 - 50; http://dx.doi.org/10.1038/nm1592; PMID: 17558415
   PubMed Web of Science ®Google Scholar
• Forbes EK, Sander C, Ronan EO, McShane H, Hill AV, Beverley PC, Tchilian EZ. Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice. J Immunol 2008; 181:4955 - 64; http://dx.doi.org/10.4049/jimmunol.181.7.4955; PMID: 18802099
   PubMed Web of Science ®Google Scholar
• Pedersen G, Major D, Roseby S, Wood J, Madhun AS, Cox RJ. Matrix-M adjuvanted virosomal H5N1 vaccine confers protection against lethal viral challenge in a murine model. Influenza Other Respir Viruses 2011; 5:426 - 37; http://dx.doi.org/10.1111/j.1750-2659.2011.00256.x; PMID: 21668670
   PubMed Web of Science ®Google Scholar
• Kannanganat S, Ibegbu C, Chennareddi L, Robinson HL, Amara RR. Multiple-cytokine-producing antiviral CD4 T cells are functionally superior to single-cytokine-producing cells. J Virol 2007; 81:8468 - 76; http://dx.doi.org/10.1128/JVI.00228-07; PMID: 17553885
   PubMed Web of Science ®Google Scholar
• Tangye SG, Ferguson A, Avery DT, Ma CS, Hodgkin PD. Isotype switching by human B cells is division-associated and regulated by cytokines. J Immunol 2002; 169:4298 - 306; http://dx.doi.org/10.4049/jimmunol.169.8.4298; PMID: 12370361
   PubMed Web of Science ®Google Scholar
• Hasbold J, Corcoran LM, Tarlinton DM, Tangye SG, Hodgkin PD. Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation. Nat Immunol 2004; 5:55 - 63; http://dx.doi.org/10.1038/ni1016; PMID: 14647274
   PubMed Web of Science ®Google Scholar
• Bungener L, Geeraedts F, Ter Veer W, Medema J, Wilschut J, Huckriede A. Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection. Vaccine 2008; 26:2350 - 9; http://dx.doi.org/10.1016/j.vaccine.2008.02.063; PMID: 18400340
   PubMed Web of Science ®Google Scholar
• Moran TM, Isobe H, Fernandez-Sesma A, Schulman JL. Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol 1996; 70:5230 - 5; PMID: 8764032
   PubMed Web of Science ®Google Scholar
• Huber VC, McKeon RM, Brackin MN, Miller LA, Keating R, Brown SA, Makarova N, Perez DR, Macdonald GH, McCullers JA. Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol 2006; 13:981 - 90; http://dx.doi.org/10.1128/CVI.00156-06; PMID: 16960108
   PubMed Web of Science ®Google Scholar
• Galli G, Medini D, Borgogni E, Zedda L, Bardelli M, Malzone C, Nuti S, Tavarini S, Sammicheli C, Hilbert AK, et al. Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels. Proc Natl Acad Sci U S A 2009; 106:3877 - 82; http://dx.doi.org/10.1073/pnas.0813390106; PMID: 19237568
   PubMed Web of Science ®Google Scholar
• Moris P, van der Most R, Leroux-Roels I, Clement F, Dramé M, Hanon E, Leroux-Roels GG, Van Mechelen M. H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol 2011; 31:443 - 54; http://dx.doi.org/10.1007/s10875-010-9490-6; PMID: 21174144
   PubMed Web of Science ®Google Scholar
• Madhun AS, Haaheim LR, Nilsen MV, Cox RJ. Intramuscular Matrix-M-adjuvanted virosomal H5N1 vaccine induces high frequencies of multifunctional Th1 CD4+ cells and strong antibody responses in mice. Vaccine 2009; 27:7367 - 76; http://dx.doi.org/10.1016/j.vaccine.2009.09.044; PMID: 19781678
   PubMed Web of Science ®Google Scholar
• Cox RJ, Pedersen G, Madhun AS, Svindland S, Sævik M, Breakwell L, Hoschler K, Willemsen M, Campitelli L, Nøstbakken JK, et al. Evaluation of a virosomal H5N1 vaccine formulated with Matrix M™ adjuvant in a phase I clinical trial. Vaccine 2011; 29:8049 - 59; http://dx.doi.org/10.1016/j.vaccine.2011.08.042; PMID: 21864624
   PubMed Web of Science ®Google Scholar
• Pedersen GK, Madhun AS, Breakwell L, Hoschler K, Sjursen H, Pathirana RD, Goudsmit J, Cox RJ. T-helper 1 cells elicited by H5N1 vaccination predict seroprotection. J Infect Dis 2012; 206:158 - 66; http://dx.doi.org/10.1093/infdis/jis330; PMID: 22551811
   PubMed Web of Science ®Google Scholar
• Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993; 260:547 - 9; http://dx.doi.org/10.1126/science.8097338; PMID: 8097338
   PubMed Web of Science ®Google Scholar
• Shi Y, Liu CH, Roberts AI, Das J, Xu G, Ren G, Zhang Y, Zhang L, Yuan ZR, Tan HS, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 2006; 16:126 - 33; http://dx.doi.org/10.1038/sj.cr.7310017; PMID: 16474424
   PubMed Web of Science ®Google Scholar
• Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S, Allen T, Perez DR, Whitsett JA, Dunussi-Joannopoulos K, et al. GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med 2011; 184:259 - 68; http://dx.doi.org/10.1164/rccm.201012-2036OC; PMID: 21474645
   PubMed Web of Science ®Google Scholar
• Magnusson SE, Reimer JM, Karlsson KH, Lilja L, Bengtsson KL, Stertman L. Immune enhancing properties of the novel Matrix-M™ adjuvant leads to potentiated immune responses to an influenza vaccine in mice. Vaccine 2013; 31:1725 - 33; http://dx.doi.org/10.1016/j.vaccine.2013.01.039; PMID: 23384754
   PubMed Web of Science ®Google Scholar
• Pichichero ME. Improving vaccine delivery using novel adjuvant systems. Hum Vaccin 2008; 4:262 - 70; http://dx.doi.org/10.4161/hv.4.4.5742; PMID: 18398303
   PubMed Web of Science ®Google Scholar
• Heijmans S, De Meulemeester M, Reynders P, Giet D, Demanet E, Devresse PY, Icardi G, Dramé M, Roman F, Gillard P. Immunogenicity profile of a 3.75-mug hemagglutinin pandemic rH5N1 split virion AS03A-adjuvanted vaccine in elderly persons: a randomized trial. J Infect Dis 2011; 203:1054 - 62; http://dx.doi.org/10.1093/infdis/jiq174; PMID: 21450995
   PubMed Web of Science ®Google Scholar
• Pathirana RD, Bredholt G, Akselsen PE, Pedersen GK, Cox RJA. A(H1N1)pdm09 vaccination of health care workers: improved immune responses in low responders following revaccination. J Infect Dis 2012; 206:1660 - 9; http://dx.doi.org/10.1093/infdis/jis589; PMID: 22969149
   PubMed Web of Science ®Google Scholar
• Jul-Larsen Å, Madhun AS, Brokstad KA, Montomoli E, Yusibov V, Cox RJ. The human potential of a recombinant pandemic influenza vaccine produced in tobacco plants. Hum Vaccin Immunother 2012; 8:653 - 61; http://dx.doi.org/10.4161/hv.19503; PMID: 22634440
   PubMed Web of Science ®Google Scholar
• Roman F, Clément F, Dewé W, Walravens K, Maes C, Willekens J, De Boever F, Hanon E, Leroux-Roels G. Effect on cellular and humoral immune responses of the AS03 adjuvant system in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials. Clin Vaccine Immunol 2011; 18:835 - 43; http://dx.doi.org/10.1128/CVI.00480-10; PMID: 21450978
   PubMed Web of Science ®Google Scholar
• Saraiva M, O’Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10:170 - 81; http://dx.doi.org/10.1038/nri2711; PMID: 20154735
   PubMed Web of Science ®Google Scholar
• Lee LY, Ha LA, Simmons C, de Jong MD, Chau NV, Schumacher R, Peng YC, McMichael AJ, Farrar JJ, Smith GL, et al. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest 2008; 118:3478 - 90; PMID: 18802496
   PubMed Web of Science ®Google Scholar
• Kabilan L, Andersson G, Lolli F, Ekre HP, Olsson T, Troye-Blomberg M. Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro. Eur J Immunol 1990; 20:1085 - 9; http://dx.doi.org/10.1002/eji.1830200521; PMID: 2113474
   PubMed Web of Science ®Google Scholar
• Jung T, Schauer U, Heusser C, Neumann C, Rieger C. Detection of intracellular cytokines by flow cytometry. J Immunol Methods 1993; 159:197 - 207; http://dx.doi.org/10.1016/0022-1759(93)90158-4; PMID: 8445253
   PubMed Web of Science ®Google Scholar
• Gijzen K, Liu WM, Visontai I, Oftung F, van der Werf S, Korsvold GE, Pronk I, Aaberge IS, Tütto A, Jankovics I, et al. Standardization and validation of assays determining cellular immune responses against influenza. Vaccine 2010; 28:3416 - 22; http://dx.doi.org/10.1016/j.vaccine.2010.02.076; PMID: 20206285
   PubMed Web of Science ®Google Scholar
• Cox RJ, Madhun AS, Hauge S, Sjursen H, Major D, Kuhne M, Höschler K, Saville M, Vogel FR, Barclay W, et al. A phase I clinical trial of a PER.C6 cell grown influenza H7 virus vaccine. Vaccine 2009; 27:1889 - 97; http://dx.doi.org/10.1016/j.vaccine.2009.01.116; PMID: 19368768
   PubMed Web of Science ®Google Scholar
• Pedersen G, Halstensen A, Sjursen H, Naess A, Kristoffersen EK, Cox RJ. Pandemic influenza vaccination elicits influenza-specific CD4+ Th1-cell responses in hypogammaglobulinaemic patients: four case reports. Scand J Immunol 2011; 74:210 - 8; http://dx.doi.org/10.1111/j.1365-3083.2011.02561.x; PMID: 21438900
   PubMed Web of Science ®Google Scholar
• Rowe T, Abernathy RA, Hu-Primmer J, Thompson WW, Lu X, Lim W, Fukuda K, Cox NJ, Katz JM. Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. J Clin Microbiol 1999; 37:937 - 43; PMID: 10074505
   PubMed Web of Science ®Google Scholar
• Nicholson KG, Colegate AE, Podda A, Stephenson I, Wood J, Ypma E, Zambon MC. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet 2001; 357:1937 - 43; http://dx.doi.org/10.1016/S0140-6736(00)05066-2; PMID: 11425416
   PubMed Web of Science ®Google Scholar
• Stephenson I, Wood JM, Nicholson KG, Zambon MC. Sialic acid receptor specificity on erythrocytes affects detection of antibody to avian influenza haemagglutinin. J Med Virol 2003; 70:391 - 8; http://dx.doi.org/10.1002/jmv.10408; PMID: 12767002
   PubMed Web of Science ®Google Scholar
• Banzhoff A, Gasparini R, Laghi-Pasini F, Staniscia T, Durando P, Montomoli E, Capecchi PL, di Giovanni P, Sticchi L, Gentile C, et al. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One 2009; 4:e4384; http://dx.doi.org/10.1371/journal.pone.0004384; PMID: 19197383
   PubMed Web of Science ®Google Scholar