Safety review: Squalene and thimerosal in vaccines

Therapie

Volumn 65, Issue 6, 2010, Pages 533-541

  Montana, Marc ^a   Verhaeghe, Pierre ^a   Ducros, Caroline ^a   Terme, Thierry ^a   Vanelle, Patrice ^a,b   Rathelot, Pascal ^a,b  

^a AIX MARSEILLE UNIVERSITY   (France)

^b ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE   (France)

Author keywords

Adjuvants; Review; Squalene; Thimerosal

Indexed keywords

CELPAVAN; GRIPGUARD; INFLUENZA VACCINE; PANENZA; PANVAX; SQUALENE; THIOMERSAL; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ANAPHYLAXIS; APPENDICITIS; ARTHRALGIA; AUTISM; AUTOIMMUNE DISEASE; CLINICAL TRIAL (TOPIC); CONVULSION; DELAYED HYPERSENSITIVITY; DRUG EFFICACY; DRUG EXPOSURE; DRUG FORMULATION; DRUG SAFETY; DRUG TOLERABILITY; ECTOPIC PREGNANCY; FACIAL NERVE PARALYSIS; FATIGUE; FETUS DEATH; FEVER; FRACTURE; GASTROENTERITIS; GUILLAIN BARRE SYNDROME; HEADACHE; HUMAN; INFLUENZA VIRUS A H1N1; INJECTION SITE INDURATION; INJECTION SITE INFLAMMATION; INJECTION SITE PAIN; INJECTION SITE SWELLING; INTERVERTEBRAL DISK DISEASE; LYMPHOMA; MULTIPLE SCLEROSIS; MYALGIA; NONHUMAN; OSTEOARTHRITIS; PNEUMONIA; POSTMARKETING SURVEILLANCE; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SIDE EFFECT; SPONTANEOUS ABORTION; STILLBIRTH;

EID: 79954549943     PISSN: 00405957     EISSN: None     Source Type: Journal    
DOI: 10.2515/therapie/2010069     Document Type: Review

References (93)

1. Cate TR. Clinical manifestation and consequence of influenza. Am J Med 1987; 82: 15-9
2. Fraser C, Donnelly CA, Cauchemez S, et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science 2009; 324: 1557-61
3. World Health Organization. Pandemic H1N1 2009-Update 89, http://www. who.int/csr/don/2010-02-26/en/index.html
4. Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine 2001; 19: 2673-80 (Pubitemid 32234288)
5. Grubeck-Loebenstein B, Della Bella S, Iorio AM, et al. Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 2009; 21: 201-9
6. Phair J, Kauffman CA, Bjornson A, et al. Failure to respond to influenza vaccine in the aged: correlation with B-cell number and function. J Lab Clin Med 1978; 92: 822-8 (Pubitemid 9058671)
7. Keren G, Segev S, Morag A, et al. Failure of influenza vaccination in the aged. J Med Virol 1988; 25: 85-9
8. Ford S, Clews G. DH director of immunisation tells nurses they have a 'duty' to have swine flu jab. Nursing Time.net, http://www. nursingtimes.net/ whats-new-in-nursing/swine-flu/dhdirector- of-immunisation-tells-nurses-they- have-a-dutyto- have-swine-flu-jab/5005221.article
9. Chor JS, Ngai KL, Goggins WB, et al. Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys. BMJ 2009 Aug 25; 339b: 3398
10. Fox CB. Squalene emulsions for parenteral vaccine and drug delivery. Molecules 2009; 14: 3286-312
11. Schultze V, D'Agosto V, Wack A, et al. Safety of MF59 adjuvant. Vaccine 2008; 26: 3209-22
12. Alam SQ, Brossard J, Mackinney G. Detection and estimation of squalene in leaves. Nature 1962; 194: 479-80
13. Deiana M, Corongui FP, Dessi MA, et al. NMR determination of site-specific deuterium distribution (SNIF-NMR) in squalene from different sources. Magn Reson Chem 2001; 39: 29-32
14. Kelly GS. Squalene and its potential clinical uses. Alter Med Rev 1999; 4: 29-36 (Pubitemid 29205159)
15. Jenck JF, Agterberg F, Droescher MJ. Products and processes for a sustainable chemical industry: a review of achievements and prospects. Green Chem 2004; 6: 544-56 (Pubitemid 39636064)
16. Allison AC. Squalene and squalane emulsions as adjuvants. Methods 1999; 19: 87-93 (Pubitemid 29497757)
17. Dupuis M,Mc Donald DM, Ott G. Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection in mice. Vaccine 1999; 18: 434-9 (Pubitemid 29462599)
18. Seubert A, Monaci E, Pizza M, et al. The adjuvants aluminium hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differenciation toward dendritic cells. J Immunol 2008; 180: 5402-12
19. Valensi JP, Carlson JR, Van Nest G. Systemic cytokine profiles in BALB/c mice immunized with trivalent influenza vaccine containing MF59 oil emulsion and other advanced adjuvants. J Immunol 1994; 153: 4029-39
20. Tritto E, Mosca F, De Gregorio E. Mechanism of action of licensed vaccine adjuvants. Vaccine 2009; 27: 3331-4
21. Pellegrini M, Nicolay U, Lindert K, et al. MF59-adjuvanted versus nonadjuvanted influenza vaccines: integrated analysis from a large safety database. Vaccine 2009; 27: 6959-65
22. 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 (Pubitemid 36438758)
23. Baldo V, Baldovin T, Floreani A, et al. MF59-adjuvanted influenza vaccine confers superior immunogenicity in adult subjects (18-60 years of age) with chronic diseases who are at risk of post-influenza complications. Vaccine 2007; 25: 3955-61 (Pubitemid 46616991)
24. Frey S, Poland G, Percell S, et al. Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine 2003; 21: 4234-7 (Pubitemid 37130269)
25. Vesikari T, Pellegrini M, Karvonen A, et al. Enhanced immunogenicity of seasonal influenza vaccines in young children using MF59 adjuvant. Pediatr Infect Dis J 2009; 28: 563-71
26. Nicholson KG, Colegate AE, Podda A, et al. Safety and antigenicity of nonadjuvanted 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 (Pubitemid 32568336)
27. De Donato S, Granoff D, Minutello M, et al. Safety and immunogenicity of MF59-adjuvanted influenza vaccine in the elderly. Vaccine 1999; 17: 3094-101 (Pubitemid 29366990)
28. Minutello M, Senatore F, Cecchinelli G, et al. Safety and immunogenicity of an inactivated subunit influenza virus vaccine combined with MF59 adjuvant emulsion in elderly subjects, immunized for three consecutive influenza seasons. Vaccine 1999; 17: 99-104 (Pubitemid 28494106)
29. Baldo V, Menegon T, Bonello C, et al. Collaborative Group. Comparison of three different influenza vaccines in institutionalised elderly. Vaccine 2001; 19: 3472-5 (Pubitemid 32710298)
30. Gasparini R, Pozzi T, Montomoli E, et al. Increased immunogenicity of the MF59®adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects. Eur J Epidemiol 2001; 17: 135-40 (Pubitemid 32900039)
31. Squarcione S, Sgricia S, Biasio LR, et al. Comparison of the reactogenicity and immunogenicity of a split and a subunit-adjuvanted influenza vaccine in elderly subjects. Vaccine 2003; 21: 1268-74 (Pubitemid 36139959)
32. Banzhoff A, Gasparini R, Laghi-Pasini F, et al. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One 2009 Feb; 4: e4384
33. Tsai T, Kyaw MH, Novicki D, et al. Exposure to MF59-adjuvanted influenza vaccines during pregnancy-A retrospective analysis. Vaccine 2010; 28: 1877-80
34. Chu DW, Hwang SJ, Lim FS, et al. Immunogenicity and tolerability of an AS03(A)-adjuvanted prepandemic influenza vaccine: a phase III study in a large population of Asian adults. Vaccine 2009; 27: 7428-35
35. Leroux-Roels I, Borkowski A, Vanwolleghem T, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007; 370: 580-9 (Pubitemid 47247854)
36. 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 2010; 28: 849-57
37. Rümke HC, Bayas JM, de Juanes JR, 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
38. Roman F, Vaman T, Gerlach B, et al. 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
39. Ballester A, Garcés-Sánchez M, Planelles Cantarino MV, et al. Pediatric safety evaluation of an AS-adjuvanted H5N1 prepandemic candidate vaccine in children aged 3-9 years: a phase II study. IJID 2008; 12: 146
40. Bhakdi S, Lackner K, Doerr HW. Possible hidden hazards of mass vaccination against new influenza A/H1N1: have the cardiovascular risks been adequately weighed? Med Microbiol Immunol 2009; 198: 205-9
41. Sanofi Pasteur, Inc. Panenzar® and Humenzar® Influenza A (H1N1) vaccines demonstrate robust immune response after one dose [media release]. 2009 Oct 8, http://en.sanofi-aventis.com/binaries/20091008-h1n1-eur-trial-results- en-tcm28-26516.pdf
42. Pharmacovigilance of A (H1N1) influenza vaccines. 2010 Feb 11, http:// www.icf.uab.es/informacion/EI-Vacunes-Agencies-eng.pdf
43. Shaw CA, Petrik MS. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorg Biochem 2009; 103: 1555-62
44. Carlson BC, Jansson AM, Larsson A, et al. The endogenous adjuvant squalene can induce a chronic T-cell-mediated arthritis in rats. American Journal of Pathology 2000; 156: 2057-65 (Pubitemid 30641773)
45. Holm BC, Svelander L, Bucht A, et al. The arthritogenic adjuvant squalene does not accumulate in joints, but gives rise to pathogenic cells in both draining and non-draining lymph nodes. Clin Exp Immunol 2002; 127: 430-5 (Pubitemid 34437814)
46. Hughes RA, Cornblatt DR. Guillain-Barre syndrome. Lancet 2005; 366: 1653-66
47. Haber P, DeStefano F, Angulo FJ, et al. Guillain-Barre syndrome following influenza vaccination. JAMA 2004; 292: 2478-81 (Pubitemid 39552672)
48. Souayah N, Nasar A, Suri MF, et al. Guillain-Barre syndrome after vaccination in United States a report from the CDC/FDA vaccine adverse event reporting system. Vaccine 2007; 25: 8101
49. Sivadon-Tardy V, Orlikowski D, Porcher R, et al. Guillain-Barre syndrome and influenza virus infection. Clin Infect Dis 2009; 48: 48-56
50. Tam CC, O'Brien SJ, Petersen I, et al. Guillain-Barre syndrome and preceding infection with campylobacter, influenza and Epstein-Barr virus in the general practice research database. PLoS One 2007 Apr4; 2: e344
51. Stowe J, Andrews N, Wise L, et al. Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and inflenzalike illness using the United Kingdom general practice Research database. Am J Epidemiol 2009; 169: 382-8
52. Gherardi RK. Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome. Rev Neurol 2003; 159: 162-4 (Pubitemid 36292557)
53. Asa PB,Wilson RB, Garry RF. Antibodies to squalene in recipients of anthrax vaccine. Exp Mol Pathol 2002; 73: 19-27 (Pubitemid 34775454)
54. Asa PB, Cao Y, Garry RF. Antibodies to squalene in GulfWar syndrome. Exp Mol Pathol 2000; 68: 55-64
55. Asa PB, Cao Y, Garry RF. Reply Exp Mol Pathol 2000; 68: 197-8
56. Kuroda Y, Nacionales DC, Akaogi J, et al. Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine. Biomed Pharmacother 2004; 58: 325-37 (Pubitemid 38759732)
57. Satoh M, Kuroda Y, Yoshida H, et al. Induction of lupus autoantibodies by adjuvants. J Autoimmun 2003; 21: 1-9 (Pubitemid 36871681)
58. Lorentzen JC. Identification of arthritogenic adjuvants of self and foreign origin. Scand J Immunol 1999; 49: 45-50 (Pubitemid 29052436)
59. Gajkowska B, Smialek M, Ostrowski RP, et al. The experimental squalene encephaloneuropathy in the rat. Exp Toxicol Pathol 1999; 51: 75-80 (Pubitemid 29046566)
60. Spanggord RJ, Sun M, Lim P, et al. Enhancement of an analytical method for the determination of squalene in anthrax vaccine adsorbed formulations. J Pharm Biomed Anal 2006; 42: 494-9 (Pubitemid 44375101)
61. Spanggord RJ, Wu B, Sun M, et al. Development and application of an analytical method for the determination of squalene in formulations of anthrax vaccine adsorbed. J Pharm Biomed Anal 2002; 29: 183-93 (Pubitemid 34621280)
62. Alving CR, Grabenstein JD. Re: Antibodies to squalene in Gulf War Syndrome. Exp Mol Pathol 2000; 68: 196-8
63. 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: 1010-3 (Pubitemid 44518969)
64. Matyas GR, RaoM, Pittman PR, et al. Detection of antibodies to squalene: III. Naturally occurring antibodies to squalene in humans and mice. J Immunol Methods 2004; 286: 47-67 (Pubitemid 38490396)
65. Matyas GR, Rao M, Alving CR. Induction and detection of antibodies to squalene. II. Optimization of the assay for murine antibodies. J Immunol Methods 2002; 267: 119-29 (Pubitemid 34880026)
66. Matyas GR, Wassef NM, Rao M, et al. Induction and detection of antibodies to squalene. J Immunol Methods 2000; 245: 1-14
67. Phillips CJ, Matyas GR, Hansen CJ, et al. Antibodies to squalene in US Navy Persian Gulf War veterans with chronic multisymptom illness. Vaccine 2009; 27: 3921-6
68. Haute Autorité de Santé. Actualisation de l'avis relatif aux recommandations sur les priorités sanitaires d'utilisation des vaccins pandémiques dirigés contre le virus grippal A(H1N1), http://www.hcsp.fr/docspdf/ avisrapports/hcspa20091002-H1N1.pdf
69. Bernard S, Enayati A, Redwood L, et al. Autism: a novel form of mercury poisoning. Med Hypotheses 2001; 56: 462-71 (Pubitemid 32397879)
70. Bernard S, Enayati A, Roger H, et al. The role of mercury in the pathogenesis of autism. Mol Psychiatry 2002; 7: S42-3
71. Geier, MR, Geier, DA. Neurodevelopmental disorders after thimerosalcontaining vaccines: a brief communication. Exp Biol Med (Maywood) 2003; 228: 660-4 (Pubitemid 37163255)
72. Geier DA, King PG, Sykes LK, et al. A comprehensive review of mercury provoked autism. Indian J Med Res 2008; 128: 383-411
73. Redwood L, Bernard S, Brown D. Predicted mercury concentrations in hair from infant immunizations: cause for concern. Neurotoxicology 2001; 22: 691-4
74. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics 2001; 107: 1147-54 (Pubitemid 32440625)
75. Pichichero ME, Gentile A, Giglio N, et al.Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines. Pediatrics 2008, 121: 208-14
76. Pichichero ME, Cernichiari E, Lopreiato J, et al. Mercury concentrations and metabolism in infants receiving vaccines containing thimesoral: a descriptive study. Lancet 2002; 360: 1737-41 (Pubitemid 35447903)
77. Henderson DC. Mercury in vaccines-reassuring news. Lancet 2002; 360: 1711-2
78. Thompson WW, Price C, Goodson B, et al. Early thimesoral exposure and neuropsychological outcomes at 7 and 10 years. N Eng J Med 2007; 357: 1281-92 (Pubitemid 47481450)
79. Stehr-Green P, Tull P, Stellfeld M, et al. Autism and thimerosal-containing vaccines: lack of consistent evidence for an association. Am J Prev Med 2003; 25: 101-6 (Pubitemid 36918347)
80. Madsen KM, Lauritsen MB, Pedersen CB, et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish populationbased data. Pediatrics 2003; 112: 604-6 (Pubitemid 37082114)
81. Fombonne E, Zakarian R, Bennett A, et al. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics 2006; 118: e139-50
82. Verstraeten T, Davis RL, DeStefano F, et al. Safety of thimesoral-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics 2003; 112: 1039-48 (Pubitemid 37339554)
83. Hviid A, Stellfeld M, Wohlfahrt J, et al. Association between thimerosalcontaining vaccine and autism. JAMA 2003; 290: 1763-6
84. Heron J, Golding J. Thimerosal exposure in infants and developmental disorders: a prospective cohort study in the United Kingdom does not support a causal association. Pediatrics 2004; 114: 577-83 (Pubitemid 41529509)
85. Immunization safety review committee. Report of the Institute of Medicine. Immunization safety review: vaccines and autism. Washington, DC: Institute of Medicine, The National Academy press; 2004
86. Blaxill MF, Redwood L, Bernard S. Thimerosal and autism? A plausible hypothesis that should not be dismissed. Med Hypotheses 2004; 62: 788-94 (Pubitemid 38530342)
87. Stajich GV, Lopez GP, Harry SW, et al. Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr 2000; 136: 679-81 (Pubitemid 30318401)
88. Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in Iraq. Science 1973; 181: 230-41
89. Joint Statement of the American Academy of Pediatrics (AAP) and the United States Public Health Services (USPHS) [editorial]. Pediatrics 1999; 104: 568-9
90. Clements CJ, Ball LK, Ball R, et al. Thiomersal in vaccines: is removal warranted? Drug Saf 2001; 24: 567-74 (Pubitemid 32656070)
91. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229-33
92. Hessel L. Mercury in vaccines. Bull Acad Natl Med 2003; 187: 1501-10 (Pubitemid 39005353)
93. Agence Française de Sécurité Sanitaire des Produits de Santé. Le thiomersal , http://www.afssaps.fr/var/afssaps-site/storage/ original/application/52e910f9513961b1a638e4a2d4212ea1.pdf