An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants

Expert Review of Vaccines

Volumn 12, Issue 7, 2013, Pages 747-758

  Fox, Christopher B ^a   Haensler, Jean ^b  

^a IDRI   (United States)

^b SANOFI PASTEUR   (France)

Author keywords

adjuvant safety and immunogenicity; AS03; emulsion; MF59

Indexed keywords

ADJUVANT; ANTIGEN; CIRCUMSPOROZOITE PROTEIN; INFLUENZA VACCINE; LIVE VACCINE; MIFAMURTIDE;

CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG INFORMATION; DRUG MANUFACTURE; DRUG POTENTIATION; DRUG SAFETY; DRUG STABILITY; DRUG SURVEILLANCE PROGRAM; EMULSION; ERYTHEMA; FATIGUE; FEVER; HEADACHE; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; INCIDENCE; INFLUENZA VIRUS A H1N1; INFLUENZA VIRUS A H5N1; INJECTION SITE REACTION; MALAISE; MYALGIA; PAIN; PHASE 2 CLINICAL TRIAL (TOPIC); PLASMODIUM FALCIPARUM; POSTMARKETING SURVEILLANCE; PRIORITY JOURNAL; REVIEW; SWELLING; TRANSITION TEMPERATURE; VACCINATION;

ADJUVANTS, IMMUNOLOGIC; ALPHA-TOCOPHEROL; CLINICAL TRIALS AS TOPIC; DRUG COMBINATIONS; EMULSIONS; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; POLYSORBATES; PRODUCT SURVEILLANCE, POSTMARKETING; SQUALENE; VACCINES;

EID: 84880872387     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2013.811188     Document Type: Review

References (151)

1. Whitmore ER. Lipovaccines, with special reference to public health work. Am. J. Public Health (N. Y). 9(7), 504-507 (1919
2. Lewis PA, Dodge FW. The sterilization of lipovaccines. J. Exp. Med. 31(2), 169-175 (1920
3. Freund J, Bonanto MV. The effect of paraffin oil, lanolin-like substances and killed tubercle bacilli on immunization with diphtheric toxoid and bact. Typhosum. J. Immunol. 48, 325-334 (1944
4. Freund J, Casals J, Hosmer EP. Sensitization and antibody formation after injection of tubercle bacilli and paraffin oil. Proc. Soc. Exp. Biol. Med. 37, 509-513 (1937
5. Edelman R. Vaccine adjuvants. Rev. Infect. Dis. 2(3), 370-383 (1980
6. Stewart-Tull DES. Freund's complete and incomplete adjuvants, preparation, and quality control standards for experimental laboratory animals use. In: Vaccine Adjuvants: Methods and Protocols. Davies G (Ed.). Springer, NY, USA 59-72 (2010
7. Hilleman MR. Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology. Immunol. Rev. 170, 7-27 (1999
8. Allison AC, Byars NE. Syntex adjuvant formulation. Res. Immunol. 143(5), 519-525 (1992
9. Ott G, Radhakrishnan R, Fang JH, Hora M. The adjuvant MF59: A 10-year perspective. Methods Mol. Med. 42, 211-228 (2000
10. Fox CB. Squalene emulsions for parenteral vaccine and drug delivery. Molecules 14(9), 3286-3312 (2009
11. 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. 101(12), 4490-4500 (2012
12. Fox CB, Huynh C, O'Hara MK, Onu A. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania. Vaccine 31(12), 1633-1640 (2013
13. European Medicines Agency. CHMP assessment report for Pandemrix. London, UK (2009
14. 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. In: Vaccine design: The subunit and adjuvant approach. Powell MF, Newman MJ (Eds). Plenum Press, New York, NY, USA 277-296 (1995
15. Bachmann MF, Jennings GT. Vaccine delivery: A matter of size, geometry, kinetics and molecular patterns. Nat. Rev. Immunol. 10(11), 787-796 (2010
16. Novartis. New Zealand Data Sheet. Fluad, Auckland, NZ, USA (2011
17. European Medicines Agency. European public assessment report for Pandemrix. London, UK (2012
18. O'Hagan DT, Ott GS, De Gregorio E, Seubert A. The mechanism of action of MF59 -An innately attractive adjuvant formulation. Vaccine 30(29), 4341-4348 (2012
19. Morel S, Didierlaurent A, Bourguignon P et al. Adjuvant System AS03 containing α-Tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 29(13), 2461-2473 (2011
20. Seubert A, Calabro S, Santini L 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. USA 108(27), 11169-11174 (2011
21. 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. USA 108(7), 2927-2932 (2011
22. Hui GS, Hashimoto CN. Adjuvant formulations possess differing efficacy in the potentiation of antibody and cell mediated responses to a human malaria vaccine under selective immune genes knockout environment. Int. Immunopharmacol. 8(7), 1012-1022 (2008
23. 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. 110, 4429 (2013
24. Garçon N, Vaughn DW, Didierlaurent AM. Development and evaluation of AS03, an Adjuvant System containing a-Tocopherol and squalene in an oil-inwater emulsion. Expert Rev. Vaccines 11(3), 349-366 (2012
25. O'Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD. The history of MF59(®) adjuvant: A phoenix that arose from the ashes. Expert Rev. Vaccines 12(1), 13-30 (2013
26. Walker WT, Faust SN. Monovalent inactivated split-virion AS03-Adjuvanted pandemic influenza A (H1N1) vaccine. Expert Rev. Vaccines 9(12), 1385-1398 (2010
27. Whitaker J, Rouphael N, Mulligan MJ. MF59: An oil-in-water adjuvant. In: Emulsion-Based Vaccine Adjuvants. Fox CB, Carter D, Reed SG (Eds). Future Medicine, London, UK, 7-19 (2012
28. Cox M. Update on clinical trials evaluation of adjuvanted rHA(H5) vaccines. Presented at: 7th WHO Meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials. 17-18 February 2011, Geneva, Switzerland
29. Foglia G, Sheldon E. Emulsion-Adjuvanted clade 2 influenza A/H5N1 vaccine: A randomized, placebo-controlled antigen and adjuvant dose-ranging Phase I clinical trial in healthy adults. Presented at: 12th Annual Conference on Vaccines Research. 7-9 May 2009, Baltimore, MD, USA
30. Levie K, Leroux-Roels I, Hoppenbrouwers K et al. An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces crossreactive immune responses in healthy adults. J. Infect. Dis. 198(5), 642-649 (2008
31. Del Giudice G, Fragapane E, Della Cioppa G, Rappuoli R. Aflunov®: A vaccine tailored for pre-pandemic and pandemic approaches against influenza. Expert Opin. Biol. Ther. 13(1), 121-135 (2013
32. Gasparini R, Amicizia D, Lai PL, Panatto D. Aflunov(®): A prepandemic influenza vaccine. Expert Rev. Vaccines 11(2), 145-157 (2012
33. Baras B, Bouveret N, Devaster JM et al. A vaccine manufacturer's approach to address medical needs related to seasonal and pandemic influenza viruses. Influenza Other Respi. Viruses 2(6), 251-260 (2008
34. Carter NJ, Plosker GL. Prepandemic influenza vaccine H5N1 (split virion, inactivated, adjuvanted) [Prepandrix]: A review of its use as an active immunization against influenza A subtype H5N1 virus. BioDrugs 22(5), 279-292 (2008
35. Jones T. GSK's novel split-virus adjuvanted vaccines for the prevention of the H5N1 strain of avian influenza infection. Curr. Opin. Mol. Ther. 11(3), 337-345 (2009
36. Galli G, Hancock K, Hoschler K et al. Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine. Proc. Natl Acad. Sci. USA 106(19), 7962-7967 (2009
37. Risi G, Frenette L, Langley JM et al. Immunological priming induced by a two-dose series of H5N1 influenza antigen, administered alone or in combination with two different formulations of AS03 adjuvant in adults: Results of a randomised single heterologous booster dose study at 15 months. Vaccine 29(37), 6408-6418 (2011
38. Stöhr K. Vaccinate before the next pandemic? Nature 465(7295), 161 (2010
39. Khurana S, Verma N, Yewdell JW et al. MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines. Sci. Transl. Med. 3(85), 85ra48 (2011
40. O'Hagan DT, Rappuoli R, De Gregorio E, Tsai T, Del Giudice G. MF59 adjuvant: The best insurance against influenza strain diversity. Expert Rev. Vaccines 10(4), 447-462 (2011
41. Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N. Engl. J. Med. 354(13), 1343-1351 (2006
42. Bresson JL, Perronne C, Launay O et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: Phase I randomised trial. Lancet 367(9523), 1657-1664 (2006
43. Arguedas A, Soley C, Abdelnour A et al.; Costa Rican H1N1 Vaccine Study Group. Assessment of the safety, tolerability and kinetics of the immune response to A/H1N1v vaccine formulations with and without adjuvant in healthy pediatric subjects from 3 through 17 years of age. Hum. Vaccin. 7(1), 58-66 (2011
44. Block SL, Ruiz-Palacios GM, Guerrero ML, Beygo J, Sales V, Holmes SJ. Dose-range study of MF59-Adjuvanted versus nonadjuvanted monovalent A/H1N1 pandemic influenza vaccine in six-To less than thirty-six-month-old children. Pediatr. Infect. Dis. J. 31(7), e92-e98 (2012
45. 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. 8(9), 1283-1292 (2012
46. Faenzi E, Zedda L, Bardelli M et al. One dose of an MF59-Adjuvanted pandemic A/H1N1 vaccine recruits pre-existing immune memory and induces the rapid rise of neutralizing antibodies. Vaccine 30(27), 4086-4094 (2012
47. Leroux-Roels I, Roman F, Forgus S et al. Priming with AS03 A-Adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: An open non-randomised extension of a double-blind randomised primary study. Vaccine 28(3), 849-857 (2010
48. Galli G, Medini D, Borgogni E et al. Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-Term persistence of protective antibody levels. Proc. Natl Acad. Sci. USA 106(10), 3877-3882 (2009
49. Roman F, Clé;ment F, Dewé; W et al. 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. 18(5), 835-843 (2011
50. Ortqvist A, Berggren I, Insulander M, de Jong B, Svenungsson B. Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden. Clin. Infect. Dis. 52(10), 1203-1211 (2011
51. Simpson CR, Ritchie LD, Robertson C, Sheikh A, McMenamin J. Vaccine effectiveness in pandemic influenza -primary care reporting (VIPER): An observational study to assess the effectiveness of the pandemic influenza A (H1N1)v vaccine. Health Technol. Assess. 14(34), 313-346 (2010
52. Van Buynder PG, Dhaliwal JK, Van Buynder JL et al. Protective effect of single-dose adjuvanted pandemic influenza vaccine in children. Influenza Other Respi. Viruses 4(4), 171-178 (2010
53. Andrews N, Waight P, Yung CF, Miller E. Age-specific effectiveness of an oil-in-water adjuvanted pandemic (H1N1) 2009 vaccine against confirmed infection in high risk groups in England. J. Infect. Dis. 203(1), 32-39 (2011
54. Walker WT, Faust SN. AS03 adjuvant. In: Emulsion-Based Vaccine Adjuvants. Fox CB, Carter D, Reed SG (Eds). Future Medicine, London, UK, 21-36 (2012
55. Siegrist CA, Ambrosioni J, Bel M et al.; H1N1 study group. Responses of solid organ transplant recipients to the AS03-Adjuvanted pandemic influenza vaccine. Antivir. Ther. (Lond.) 17(5), 893-903 (2012
56. Durando P, Icardi G, Ansaldi F. MF59-Adjuvanted vaccine: A safe and useful tool to enhance and broaden protection against seasonal influenza viruses in subjects at risk. Expert Opin. Biol. Ther. 10(4), 639-651 (2010
57. El Sahly H. MF59™ as a vaccine adjuvant: A review of safety and immunogenicity. Expert Rev. Vaccines 9(10), 1135-1141 (2010
58. Della Cioppa G, Vesikari T, Sokal E, Lindert K, Nicolay U. Trivalent and quadrivalent MF59(®)-Adjuvanted influenza vaccine in young children: A dose-And schedule-finding study. Vaccine 29(47), 8696-8704 (2011
59. Vesikari T, Groth N, Karvonen A, Borkowski A, Pellegrini M. MF59-Adjuvanted influenza vaccine (FLUAD) in children: Safety and immunogenicity following a second year seasonal vaccination. Vaccine 27(45), 6291-6295 (2009
60. Vesikari T, Knuf M, Wutzler P et al. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N. Engl. J. Med. 365(15), 1406-1416 (2011
61. McElhaney JE, Beran J, Devaster JM et al. S03-Adjuvanted versus non-Adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: A phase 3 randomised trial. Lancet Infect. Dis. 13(6), 485-496, 2013
62. Corey L, Langenberg AG, Ashley R et al. Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: Two randomized controlled trials. Chiron HSV Vaccine Study Group. JAMA 282(4), 331-340 (1999
63. Heineman TC, Clements-Mann ML, Poland GA et al. A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant. Vaccine 17(22), 2769-2778 (1999
64. Frey SE, Houghton M, Coates S et al. Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine 28(38), 6367-6373 (2010
65. Bernstein DI, Schleiss MR, Berencsi K et al. Effect of previous or simultaneous immunization with canarypox expressing cytomegalovirus (CMV) glycoprotein B (gB) on response to subunit gB vaccine plus MF59 in healthy CMV-seronegative adults. J. Infect. Dis. 185(5), 686-690 (2002
66. Pass RF, Zhang C, Evans A et al. Vaccine prevention of maternal cytomegalovirus infection. N. Engl. J. Med. 360(12), 1191-1199 (2009
67. McFarland EJ, Borkowsky W, Fenton T et al.; AIDS Clinical Trials Group 230 Collaborators. Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine. J. Infect. Dis. 184(10), 1331-1335 (2001
68. Spearman P, Lally MA, Elizaga M et al.; HIV Vaccine Trials Network of NIAID. A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J. Infect. Dis. 203(8), 1165-1173 (2011
69. Stoute JA, Slaoui M, Heppner DG et al. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. N. Engl. J. Med. 336(2), 86-91 (1997
70. Sun P, Schwenk R, White K et al. Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-γ. J. Immunol. 171(12), 6961-6967 (2003
71. Spring MD, Cummings JF, Ockenhouse CF et al. Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS ONE 4(4), e5254 (2009
72. Thera MA, Doumbo OK, Coulibaly D et al. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: Results of a Phase 1 randomized controlled trial. PLoS ONE 3(1), e1465 (2008
73. Thera MA, Doumbo OK, Coulibaly D et al. Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: Results of a Phase 1 randomized controlled trial. PLoS ONE 5(2), e9041 (2010
74. Cummings JF, Spring MD, Schwenk RJ et al. Recombinant Liver Stage Antigen-1 (LSA-1) formulated with AS01 or AS02 is safe, elicits high titer antibody and induces IFN-gamma/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection. Vaccine 28(31), 5135-5144 (2010
75. Thera MA, Doumbo OK, Coulibaly D et al. A field trial to assess a blood-stage malaria vaccine. N. Engl. J. Med. 365(11), 1004-1013 (2011
76. Kester KE, Cummings JF, Ofori-Anyinam O et al.; RTS,S Vaccine Evaluation Group. 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. 200(3), 337-346 (2009
77. Owusu-Agyei S, Ansong D, Asante K et al. Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. PLoS ONE 4(10), e7302 (2009
78. Regules JA, Cummings JF, Ockenhouse CF. The RTS,S vaccine candidate for malaria. Expert Rev. Vaccines 10(5), 589-599 (2011
79. Leroux-Roels I, Forgus S, De Boever F et al.; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: A randomized trial. Vaccine 31(17), 2196-2206 (2013
80. Leroux-Roels I, Koutsoukos M, Clement F et al. Strong and persistent CD4+ T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems. Vaccine 28(43), 7016-7024 (2010
81. Beran J, Hobzova L, Wertzova V et al. Safety and immunogenicity of an investigational adjuvanted hepatitis B vaccine (HB-AS02V) in healthy adults. Hum. Vaccin. 6(7), 578-584 (2010
82. Surquin M, Tielemans C, Nortier J et al. Anti-HBs antibody persistence following primary vaccination with an investigational AS02(v)-Adjuvanted hepatitis B vaccine in patients with renal insufficiency. Hum. Vaccin. 7(9), 913-918 (2011
83. Fabrizi F, Dixit V, Messa P, Martin P. Hepatitis B virus vaccine in chronic kidney disease: Improved immunogenicity by adjuvants? A meta-Analysis of randomized trials. Vaccine 30(13), 2295-2300 (2012
84. Garçon N, Van Mechelen M. Recent clinical experience with vaccines using MPL-And QS-21-containing adjuvant systems. Expert Rev. Vaccines 10(4), 471-486 (2011
85. Coler RN, Bertholet S, Moutaftsi M et al. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS ONE 6(1), e16333 (2011
86. Lambert SL, Yang CF, Liu Z et al Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A. PLoS ONE 7(12), e51618 (2012
87. Stanberry LR, Simon JK, Johnson C et al. Safety and immunogenicity of a novel nanoemulsion mucosal adjuvant W805EC combined with approved seasonal influenza antigens. Vaccine 30(2), 307-316 (2012
88. GlaxoSmithKline Biologicals. Influenza A (H5N1) virus monovalent vaccine, adjuvanted. Vaccines and Related Biological Products Advisory Committee (VRBPAC) Briefing Document. (2012
89. Banzhoff A, Haertel S, Praus M. Passive surveillance of adverse events of an MF59-Adjuvanted H1N1v vaccine during the pandemic mass vaccinations. Hum. Vaccin. 7(5), 539-548 (2011
90. Pellegrini M, Nicolay U, Lindert K, Groth N, Della Cioppa G. MF59-Adjuvanted versus non-Adjuvanted influenza vaccines: Integrated analysis from a large safety database. Vaccine 27(49), 6959-6965 (2009
91. Schultze V, D'Agosto V, Wack A, Novicki D, Zorn J, Hennig R. Safety of MF59 adjuvant. Vaccine 26(26), 3209-3222 (2008
92. Carmona A, Omend;aca F, Tejedor JC et al. Immunogenicity and safety of AS03-Adjuvanted 2009 influenza A H1N1 vaccine in children 6-35 months. Vaccine 28(36), 5837-5844 (2010
93. Waddington CS, Walker WT, Oeser C et al. Safety and immunogenicity of AS03B adjuvanted split virion versus non-Adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: Open label, randomised, parallel group, multicentre study. BMJ 340, c2649 (2010
94. Department of Health. Influenza. In: Immunisation Against Infectious Disease -The 'Green Book'. Salisbury D, Ramsay M, Noakes K (Eds). TSO, Norwich, UK, 185-215 (2011
95. Esposito S, Pugni L, Daleno C et al. Influenza A/H1N1 MF59-Adjuvanted vaccine in preterm and term children aged 6 to 23 months. Pediatrics 127(5), e1161-e1168 (2011
96. Wijnans L, Weibel D, Sturkenboom M. Adjuvanted versus nonadjuvanted influenza vaccines in young children: Comparing results from recent clinical trials. Clin. Invest, 3, 395-408 (2013
97. Calmy A, Bel M, Nguyen A et al.; H1N1 Study Group. Strong serological responses and HIV RNA increase following AS03-Adjuvanted pandemic immunization in HIV-infected patients. HIV Med. 13(4), 207-218 (2012
98. Launay O, Desaint C, Durier C et al.; ANRS 151 HIFLUVAC Study Group and the French Clinical Vaccinology Network (Ré;seau National d'Investigation Clinique en Vaccinologie REIVAC). Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIVinfected adults: A randomized, controlled trial. J. Infect. Dis. 204(1), 124-134 (2011
99. Soonawala D, Rimmelzwaan GF, Gelinck LB, Visser LG, Kroon FP. Response to 2009 pandemic influenza A (H1N1) vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination. PLoS ONE 6(1), e16496 (2011
100. Fuller JD, Craven DE, Steger KA, Cox N, Heeren TC, Chernoff D. Influenza vaccination of human immunodeficiency virus (HIV)-infected adults: Impact on plasma levels of HIV type 1 RNA and determinants of antibody response. Clin. Infect. Dis. 28(3), 541-547 (1999
101. O'Brien WA, Grovit-Ferbas K, Namazi A et al. Human immunodeficiency virus-Type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination. Blood 86(3), 1082-1089 (1995
102. Tasker SA, O'Brien WA, Treanor JJ et al. Effects of influenza vaccination in HIV-infected adults: A double-blind, placebo-controlled trial. Vaccine 16(9-10), 1039-1042 (1998
103. Meier S, Bel M, L'huillier A et al.; H1N1 Epidemiology Study Group of Geneva. Antibody responses to natural influenza A/H1N1/09 disease or following immunization with adjuvanted vaccines, in immunocompetent and immunocompromised children. Vaccine 29(19), 3548-3557 (2011
104. Rahier JF, Papay P, Salleron J et al.; European Crohn's and Colitis Organisation (ECCO). H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy. Gut 60(4), 456-462 (2011
105. van Puijenbroek EP, Broos N, van Grootheest K. Monitoring adverse events of the vaccination campaign against influenza A (H1N1) in The Netherlands. Drug Saf. 33(12), 1097-1108 (2010
106. Heikkinen T, Young J, van Beek E et al. Safety of MF59-Adjuvanted A/H1N1 influenza vaccine in pregnancy: A comparative cohort study. Am. J. Obstet. Gynecol. 207(3), 177.e1-177.e8 (2012
107. Herberts C, Melgert B, van der Laan JW, Faas M. New adjuvanted vaccines in pregnancy: What is known about their safety? Expert Rev. Vaccines 9(12), 1411-1422 (2010
108. Tsai T, Kyaw MH, Novicki D, Nacci P, Rai S, Clemens R. Exposure to MF59-Adjuvanted influenza vaccines during pregnancy -A retrospective analysis. Vaccine 28(7), 1877-1880 (2010
109. Ludvigsson JF, Zugna D, Cnattingius S, Richiardi L, Ekbom A, Ortqvist A, Persson I, Stephansson O. Influenza H1N1 accination and adverse pregnancy outcome. Eur J Epidemiol. (2013) (Epub ahead of print
110. De Wals P, Deceuninck G, Toth E et al. Risk of Guillain-Barré; syndrome following H1N1 influenza vaccination in Quebec. JAMA 308(2), 175-181 (2012
111. Dieleman J, Romio S, Johansen K, Weibel D, Bonhoeffer J, Sturkenboom M; VAESCO-GBS Case-Control Study Group. Guillain-Barre syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: Multinational case-control study in Europe. BMJ 343, d3908 (2011
112. Salmon DA, Proschan M, Forshee R et al Lancet 381(9876), 1461-1468, (2013
113. European Center for Disease Prevention and Control. Narcolepsy in association with pandemic influenza vaccination (a multi-country European epidemiological investigation). Stockholm, Sweden (2012
114. Nohynek H, Jokinen J, Partinen M et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS ONE 7(3), e33536 (2012
115. Partinen M, Saarenpää-Heikkilä O, Ilveskoski I et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS ONE 7(3), e33723 (2012
116. Heier MS, Gautvik KM, Wannag E et al. Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep. Med. doi 10.1016/j.sleep.2013.03.020 (2013) (Epub ahead of print
117. Szakacs A, Darin N, Hallbook T. Increased childhood incidence of narcolepsy in western Sweden after H1N1 influenza vaccination. Neurology 80(14), 1315-1321, (2013
118. Morris K. Implications of narcolepsy link with swine-influenza vaccine. Lancet Infect Dis 13(5), 396-397, (2013
119. European Medicines Agency. EMA recommends restricting use of Pandemrix. London, UK (2011
120. Miller E, Andrews N, Stellitano L et al. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: Retrospective analysis. BMJ 346, f794 (2013
121. Tsai TF, Crucitti A, Nacci P et al. Explorations of clinical trials and pharmacovigilance databases of MF59®-Adjuvanted influenza vaccines for associated cases of narcolepsy. Scand. J. Infect. Dis. 43(9), 702-706 (2011
122. Han F, Lin L, Warby SC et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann. Neurol. 70(3), 410-417 (2011
123. FDA. Summary minutes vaccines and related biological products advisory committee. Food and Drug Administration Center for Biologics Evaluation and Review, MD, USA (2012
124. Seppic. Montanide ISA 51 VG product description. (2012
125. Seppic. Montanide ISA 720 VG product description. (2012
126. Rodrí;guez PC, Rodrí;guez G, Gonzá;lez G, Lage A. Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy. MEDICC Rev. 12(1), 17-23 (2010
127. Graham BS, McElrath MJ, Keefer MC et al.; AIDS Vaccine Evaluation Group. Immunization with cocktail of HIVderived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity. PLoS ONE 5(8), e11995 (2010
128. Wu Y, Ellis RD, Shaffer D et al. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS ONE 3(7), e2636 (2008
129. Sabbatini P, Tsuji T, Ferran L et al. Phase I trial of overlapping long peptides from a tumor self-Antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin. Cancer Res. 18(23), 6497-6508 (2012
130. Atsmon J, Kate-Ilovitz E, Shaikevich D et al. Safety and immunogenicity of multimeric-001 -A novel universal influenza vaccine. J. Clin. Immunol. 32(3), 595-603 (2012
131. Herrera S, Ferná;ndez OL, Vera O et al. Phase I safety and immunogenicity trial of Plasmodium vivax CS derived long synthetic peptides adjuvanted with montanide ISA 720 or montanide ISA 51. Am. J. Trop. Med. Hyg. 84(2 Suppl), 12-20 (2011
132. Pierce MA, Ellis RD, Martin LB et al. Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults. Vaccine 28(10), 2236-2242 (2010
133. McCarthy JS, Marjason J, Elliott S et al. A Phase 1 trial of MSP2-C1, a blood-stage malaria vaccine containing 2 isoforms of MSP2 formulated with Montanide® ISA 720. PLoS ONE 6(9), e24413 (2011
134. Tefit JN, Serra V. Outlining novel cellular adjuvant products for therapeutic vaccines against cancer. Expert Rev. Vaccines 10(8), 1207-1220 (2011
135. Widgren K, Magnusson M, Hagstam P, Widerström M, Örtqvist Å, Einemo IM, Follin P, Lindblom A, Mäkitalo S, Wik O, Österlund A, Grünewald M, Uhnoo I, Linde A. Prevailing effectiveness of the 009 influenza A(H1N1)pdm09 vaccine during the 2010/11 season in Sweden. Euro Surveill. 18(15), 20447 (2013
136. Camin F, Bontempo L, Ziller L, Piangiolino C, Morchio G. Stable isotope ratios of carbon and hydrogen to distinguish olive oil from shark squalenesqualane. Rapid Commun. Mass Spectrom. 24(12), 1810-1816 (2010
137. Naziri E, Tsimidou MZ. Formulated squalene for food related applications. Recent Pat. Food. Nutr. Agric. 5(2), 83-104 (2013
138. Brito LA, Chan M, Baudner B et al. An alternative renewable source of squalene for use in emulsion adjuvants. Vaccine 29(37), 6262-6268 (2011
139. Fox CB, Anderson RC, Dutill TS, Goto Y, Reed SG, Vedvick TS. Monitoring the effects of component structure and source on formulation stability and adjuvant activity of oil-in-water emulsions. Colloids Surf. B. Biointerfaces 65(1), 98-105 (2008
140. Cockcroft L. Cosmetics giants agree to stop using shark oil. In: The Telegraph. Telegraph Media Group, London, UK (2008
141. Fox CB, Carter D, Baldwin SL, Reed SG. Innovations in emulsion technology. In: Emulsion-based Vaccine Adjuvants. Fox CB, Carter D, Reed SG (Eds). Future Medicine Ltd, London, 38-51 (2012
142. Ventura R, Brunner L, Heriyanto B et al. Technology transfer of an oil-in-water vaccine-Adjuvant for strengthening pandemic influenza preparedness in Indonesia. Vaccine 31(12), 1641-1645 (2013
143. Baldwin SL, Fox CB, Pallansch MA, Coler RN, Reed SG, Friede M. Increased potency of an inactivated trivalent polio vaccine with oil-in-water emulsions. Vaccine 29(4), 644-649 (2011
144. Westdijk J, Koedam P, Barro M et al. Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains. Vaccine 31(9), 1298-1304 (2013
145. Blom AG, Hilgers LA. Sucrose fatty acid sulphate esters as novel vaccine adjuvants: Effect of the chemical composition. Vaccine 23(6), 743-754 (2004
146. Heldens JG, Glansbeek HL, Hilgers LA et al. Feasibility of single-shot H5N1 influenza vaccine in ferrets, macaques and rabbits. Vaccine 28(51), 8125-8131 (2010
147. Aucouturier J, Dupuis L, Deville S, Ascarateil S, Ganne V. Montanide ISA 720 and 51: A new generation of water in oil emulsions as adjuvants for human vaccines. Expert Rev. Vaccines 1(1), 111-118 (2002
148. Aucouturier J, Dupuis L, Ganne V. Adjuvants designed for veterinary and human vaccines. Vaccine 19(17-19), 2666-2672 (2001
149. Hamouda T, Sutcliffe JA, Ciotti S, Baker JR Jr. Intranasal immunization of ferrets with commercial trivalent influenza vaccines formulated in a nanoemulsionbased adjuvant. Clin. Vaccine Immunol. 18(7), 1167-1175 (2011
150. Iseki K, Matsunaga H, Komatsu N et al. Evaluation of a new oil adjuvant for use in peptide-based cancer vaccination. Cancer Sci. 101(10), 2110-2114 (2010
151. Yamada A, Noguchi M, Komatsu N et al. Phase I clinical study of a personalized peptide vaccination available for six different human leukocyte antigen (HLA-A2, -A3, -A11, -A24, -A31 and -A33)-positive patients with advanced cancer. Exp. Ther. Med. 2(1), 109-117 (2011