Review Article | Published:

Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction

Cellular & Molecular Immunologyvolume 15pages586594 (2018) | Download Citation



Since the early 1800s vaccines have saved numerous lives by preventing lethal infections. However, during the past two decades, there has been growing awareness of possible adverse events associated with vaccinations, cultivating heated debates and leading to significant fluctuations in vaccination rates. It is therefore pertinent for the scientific community to seriously address public concern of adverse effects of vaccines to regain public trust in these important medical interventions. Such adverse reactions to vaccines may be viewed as a result of the interaction between susceptibility of the vaccinated subject and various vaccine components. Among the implicated mechanisms for these reactions is molecular mimicry. Molecular mimicry refers to a significant similarity between certain pathogenic elements contained in the vaccine and specific human proteins. This similarity may lead to immune crossreactivity, wherein the reaction of the immune system towards the pathogenic antigens may harm the similar human proteins, essentially causing autoimmune disease. In this review, we address the concept of molecular mimicry and its application in explaining post vaccination autoimmune phenomena. We further review the principal examples of the influenza, hepatitis B, and human papilloma virus vaccines, all suspected to induce autoimmunity via molecular mimicry. Finally, we refer to possible implications on the potential future development of better, safer vaccines.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Kaplan M, Meyeserian M. An immunological cross-reaction between group—a streptococcal cells and human heart tissue. Lancet 1962; 279: 706–710.

  2. 2

    Rowley D, Jenkin CR. Antigenic cross-reaction between host and parasite as a possible cause of pathogenicity. Nature 1962; 193: 151–154.

  3. 3

    Oldstone MB. Molecular mimicry and immune-mediated diseases. FASEB J 1998; 12: 1255–1265.

  4. 4

    Kanduc D, Stufano A, Lucchese G, Kusalik A. Massive peptide sharing between viral and human proteomes. Peptides 2008; 29: 1755–1766.

  5. 5

    Kanduc D. The self/nonself issue. Self Nonself 2010; 1: 255–258.

  6. 6

    Agmon-Levin N, Blank M, Paz Z, Shoenfeld Y. Molecular mimicry in systemic lupus erythematosus. Lupus 2009; 18: 1181–1185.

  7. 7

    Carpenter GDH. Mimicry, as viewed by Professor Shull. Science 1937; 85: 356–359.

  8. 8

    Damian RT. Molecular mimicry: antigen sharing by parasite and host and its consequences. Am Nat 1964; 98: 129–149.

  9. 9

    Kanduc D. Quantifying the possible cross-reactivity risk of an HPV16 vaccine. ResearchGate 2009; 8: 65–76.

  10. 10

    Trost B, Lucchese G, Stufano A, Bickis M, Kusalik A, Kanduc D. No human protein is exempt from bacterial motifs, not even one. Self Nonself 2010; 1: 328–334.

  11. 11

    Kanduc D. Peptide cross-reactivity: theoriginal sin of vaccines. Front Biosci School Ed 2012; 4: 1393–1401.

  12. 12

    Janeway CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989; 54 (Part 1): 1–13.

  13. 13

    Arango M-T, Perricone C, Kivity S, Cipriano E, Ceccarelli F, Valesini G et al. HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunol Res 2016, 1–17.

  14. 14

    Sønderstrup G, McDevitt HO. DR, DQ, and you: MHC alleles and autoimmunity. J Clin Invest 2001; 107: 795–796.

  15. 15

    Fernando MMA, Stevens CR, Walsh EC, De Jager PL, Goyette P, Plenge RM et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet [Internet] 2008; 4: e1000024. Available at:

  16. 16

    Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol 2017; 18: 76.

  17. 17

    Taneja V, Mangalem A, David CS. Genetic predisposition to autoimmune diseases conferred by the major histocompatibility complex: utility of animal models. In: Mackay IR, Rose NR (eds). The Autoimmune Diseases. Academic Press: New York, NY, 2013; pp 365–377.

  18. 18

    Dahan S, Segal Y, Shoenfeld Y. Dietary factors in rheumatic autoimmune diseases: a recipe for therapy? Nat Rev Rheumatol 2017; 13: 348–358.

  19. 19

    Perricone C, Versini M, Ben-Ami D, Gertel S, Watad A, Segel MJ et al. Smoke and autoimmunity: The fire behind the disease. Autoimmun Rev 2016; 15: 354–374.

  20. 20

    Shoenfeld N, Amital H, Shoenfeld Y. The effect of melanism and vitamin D synthesis on the incidence of autoimmune disease. Nat Clin Pract Rheumatol 2009; 5: 99–105.

  21. 21

    Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol 2014; 26: 101–107.

  22. 22

    Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009; 459: 931–939.

  23. 23

    Ahmed SS, Schur PH, MacDonald NE, Steinman L. Narcolepsy, 2009A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants. J Autoimmun 2014; 50: 1–11.

  24. 24

    Arango M-T, Kivity S, Shoenfeld Y. Is narcolepsy a classical autoimmune disease? Pharmacol Res 2015; 92: 6–12.

  25. 25

    Partinen M, Kornum BR, Plazzi G, Jennum P, Julkunen I, Vaarala O. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol 2014; 13: 600–613.

  26. 26

    Sakurai T, Mieda M, Tsujino N. The orexin system: roles in sleep/wake regulation. Ann NY Acad Sci 2010; 1200: 149–161.

  27. 27

    Katzav A, Arango MT, Kivity S, Tanaka S, Givaty G, Agmon-Levin N et al. Passive transfer of narcolepsy: anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice. J Autoimmun 2013; 45: 24–30.

  28. 28

    Singh AK, Mahlios J, Mignot E. Genetic association, seasonal infections and autoimmune basis of narcolepsy. J Autoimmun 2013; 43: 26–31.

  29. 29

    Han F, Lin L, Warby SC, Faraco J, Li J, Dong SX et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol 2011; 70: 410–417.

  30. 30

    Picchioni D, Hope CR, Harsh JR. A case–control study of the environmental risk factors for narcolepsy. Neuroepidemiology 2007; 29: 185–192.

  31. 31

    Stowe J, Andrews N, Kosky C, Dennis G, Eriksson S, Hall A et al. Risk of narcolepsy after AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in adults: a case-coverage study in England. Sleep 2016; 39: 1051–1057.

  32. 32

    Lakemedelsverket M. Occurrence of narcolepsy with cata-plexy among children and adolescents in relation to the H1N1 pandemic and Pandemrix vaccinations: results of a case inventory study by the MPA in Sweden during 2009–2010. 2011; 1: 1–20.

  33. 33

    Heier MS, Gautvik KM, Wannag E, Bronder KH, Midtlyng E, Kamaleri Y et al. Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med 2013; 14: 867–871.

  34. 34

    Dauvilliers Y, Arnulf I, Lecendreux M, Monaca Charley C, Franco P, Drouot X et al. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France. Brain 2013; 136: 2486–2496.

  35. 35

    Department of Health (DoH). Investigation of an increase in the incidence of narcolepsy in children and adolescents in 2009 and 2010 Final Report of National Narcolepsy Study Steering Committee [Internet]. 2012 Apr (cited 13 August 2017). Available at:

  36. 36

    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.

  37. 37

    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.

  38. 38

    Wang X, Yang P, Seale H, Zhang Y, Deng Y, Pang X et al. Estimates of the true number of cases of pandemic (H1N1) 2009, Beijing, China. Emerg Infect Dis 2010; 16: 1786–1788.

  39. 39

    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.

  40. 40

    Ahmed SS, Steinman L. Mechanistic insights into influenza vaccine-associated narcolepsy. Hum Vaccines Immunother 2016; 12: 3196–3201.

  41. 41

    Shoenfeld Y, George J, Peter JB. Guillain-Barré as an autoimmune disease. Int Arch Allergy Immunol. 1996; 109: 318–326.

  42. 42

    Yuki N, Hartung H-P. Guillain-Barré syndrome. N Engl J Med 2012; 366: 2294–2304.

  43. 43

    Yuki N, Taki T, Inagaki F, Kasama T, Takahashi M, Saito K et al. A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure. J Exp Med 1993; 178: 1771–1775.

  44. 44

    Wakerley BR, Yuki N. Infectious and noninfectious triggers in Guillain-Barré syndrome. Expert Rev Clin Immunol 2013; 9: 627–639.

  45. 45

    Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, Keenlyside RA, Ziegler DW, Retailliau HF et al. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976–1977. Am J Epidemiol 1979; 110: 105–123.

  46. 46

    Nachamkin I, Shadomy SV, Moran AP, Cox N, Fitzgerald C, Ung H et al. Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome. J Infect Dis 2008; 198: 226–233.

  47. 47

    Salmon DA, Vellozzi C, Chen RT, Halsey NA. Did the influenza A (H1N1) 2009 monovalent inactivated vaccines increase the risk for Guillain-Barré syndrome? Expert Rev Clin Immunol 2013; 9: 795–797.

  48. 48

    Trépo C, Chan HLY, Lok A. Hepatitis B virus infection. Lancet Lond Engl 2014; 384: 2053–2063.

  49. 49

    Maya R, Gershwin ME, Shoenfeld Y. Hepatitis B virus (HBV) and autoimmune disease. Clin Rev Allergy Immunol 2008; 34: 85–102.

  50. 50

    Zuckerman AJ. Hepatitis vaccine: a note of caution. Nature 1975; 255: 104–105.

  51. 51

    Shaw FE, Graham DJ, Guess HA, Milstien JB, Johnson JM, Schatz GC et al. Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years. Am J Epidemiol 1988; 127: 337–352.

  52. 52

    Herroelen L, de Keyser J, Ebinger G. Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine. Lancet Lond Engl 1991; 338: 1174–1175.

  53. 53

    Kaplanski G, Retornaz F, Durand J, Soubeyrand J. Central nervous system demyelination after vaccination against hepatitis B and HLA haplotype. J Neurol Neurosurg Psychiatry 1995; 58: 758–759.

  54. 54

    Gyódi E, Benczur M, Pálffy G, Tálas M, Petrányi G, Földes I et al. Association between HLA B7, DR2 and dysfunction of natural- and antibody-mediated cytotoxicity without connection with the deficient interferon production in multiple sclerosis. Hum Immunol 1982; 4: 209–217.

  55. 55

    Dyment DA, Ebers GC, Sadovnick AD. Genetics of multiple sclerosis. Lancet Neurol 2004; 3: 104–110.

  56. 56

    Shoenfeld Y, Isenberg DA. The mosaic of autoimmunity. Immunol Today 1989; 10: 123–126.

  57. 57

    Perricone C, Agmon-Levin N, Shoenfeld Y. Novel pebbles in the mosaic of autoimmunity. BMC Med 2013; 11: 101.

  58. 58

    Shoenfeld Y, Gilburd B, Abu-Shakra M, Amital H, Barzilai O, Berkun Y et al. The mosaic of autoimmunity: genetic factors involved in autoimmune diseases—2008. Isr Med Assoc J 2008; 10: 3–7.

  59. 59

    Gout O. Vaccinations and multiple sclerosis. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol 2001; 22: 151–154.

  60. 60

    Girard M. Autoimmune hazards of hepatitis B vaccine. Autoimmun Rev 2005; 4: 96–100.

  61. 61

    Grotto I, Mandel Y, Ephros M, Ashkenazi I, Shemer J. Major adverse reactions to yeast-derived hepatitis B vaccines—a review. Vaccine 1998; 16: 329–334.

  62. 62

    Vital C, Vital A, Gbikpi-Benissan G, Longy-Boursier M, Climas M-T, Castaing Y et al. Postvaccinal inflammatory neuropathy: peripheral nerve biopsy in 3 cases. J Peripher Nerv Syst 2002; 7: 163–167.

  63. 63

    Belloni C, Avanzini MA, De Silvestri A, Martinetti M, Pasi A, Coslovich E et al. No evidence of autoimmunity in 6-year-old children immunized at birth with recombinant hepatitis B vaccine. Pediatrics 2002; 110 (Part 1): e4.

  64. 64

    Monteyne P, André FE. Is there a causal link between hepatitis B vaccination and multiple sclerosis? Vaccine 2000; 18: 1994–2001.

  65. 65

    Langer-Gould A, Qian L, Tartof SY, Brara SM, Jacobsen SJ, Beaber BE et al. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol 2014; 71: 1506–1513.

  66. 66

    Demicheli V, Rivetti A, Pietrantonj CD, Clements CJ, Jefferson T. Hepatitis B vaccination and multiple sclerosis: evidence from a systematic review. J Viral Hepat 2003; 10: 343–344.

  67. 67

    DeStefano F, Verstraeten T, Jackson LA, Okoro CA, Benson P, Black SB et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60: 504–509.

  68. 68

    Ascherio A, Zhang SM, Hernán MA, Olek MJ, Coplan PM, Brodovicz K et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001; 344: 327–332.

  69. 69

    Geier DA, Geier MR. A case–control study of serious autoimmune adverse events following hepatitis B immunization. Autoimmunity 2005; 38: 295–301.

  70. 70

    Hernán MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004; 63: 838–842.

  71. 71

    Girard M. When evidence-based medicine (EBM) fuels confusion: multiple sclerosis after hepatitis B vaccine as a case in point. Med Veritas 2007; 4: 1436–1451.

  72. 72

    Bégaud B, Alpérovitch A. Vaccinations and multiple sclerosis. N Engl J Med 2001; 344: 1793–1796.

  73. 73

    Bogdanos D-P, Smith H, Ma Y, Baum H, Mieli-Vergani G, Vergani D. A study of molecular mimicry and immunological cross-reactivity between hepatitis B surface antigen and myelin mimics. Clin Dev Immunol 2005; 12: 217–224.

  74. 74

    Poirriez J. A preliminary experiment of absorption of antinuclear antibodies by the hepatitis B vaccine components, in a case of neurolupus. Vaccine 2004; 22: 3166–3168.

  75. 75

    Faure E. Multiple sclerosis and hepatitis B vaccination: could minute contamination of the vaccine by partial hepatitis B virus polymerase play a role through molecular mimicry? Med Hypotheses 2005; 65: 509–520.

  76. 76

    Soriano A, Nesher G, Shoenfeld Y. Predicting post-vaccination autoimmunity: who might be at risk? Pharmacol Res 2015; 92: 18–22.

  77. 77

    Tommasino M. The human papillomavirus family and its role in carcinogenesis. Semin Cancer Biol 2014; 26: 13–21.

  78. 78

    Iversen O-E, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K et al. Immunogenicity of the 9-valent HPV vaccine using 2-dose regimens in girls and boys vs a 3-dose regimen in women. JAMA 2016; 316: 2411–2421.

  79. 79

    Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow S-N, Apter D et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet Lond Engl 2009; 374: 301–314.

  80. 80

    Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007; 356: 1928–1943.

  81. 81

    Pellegrino P, Carnovale C, Pozzi M, Antoniazzi S, Perrone V, Salvati D et al. On the relationship between human papilloma virus vaccine and autoimmune diseases. Autoimmun Rev 2014; 13: 736–741.

  82. 82

    Baker B, Eça Guimarães L, Tomljenovic L, Agmon-Levin N, Shoenfeld Y. The safety of human papilloma virus-blockers and the risk of triggering autoimmune diseases. Expert Opin Drug Saf 2015; 14: 1387–1394.

  83. 83

    Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 2009; 302: 750–757.

  84. 84

    Cramon C, Poulsen CL, Hartling UB, Holden IK, Johansen IS. Possible adverse effects of the quadrivalent human papillomavirus vaccine in the Region of Southern Denmark: a retrospective, descriptive cohort study. Dan Med J 2017; 64.

  85. 85

    Klein NP, Hansen J, Chao C, Velicer C, Emery M, Slezak J et al. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med 2012; 166: 1140–1148.

  86. 86

    Grönlund O, Herweijer E, Sundström K, Arnheim-Dahlström L. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. J Intern Med 2016; 280: 618–626.

  87. 87

    Jefferson T, Jørgensen L. Human papillomavirus vaccines, complex regional pain syndrome, postural orthostatic tachycardia syndrome, and autonomic dysfunction—a review of the regulatory evidence from the European Medicines Agency. Indian J Med Ethics 2017; 2: 30–37.

  88. 88

    Dahan S, Shoenfeld Y. Letter to the editor—HPV vaccine and autoimmunity Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. J Intern Med 2017; 281: 313–315.

  89. 89

    Kanduc D. Penta- and hexapeptide sharing between HPV16 and Homo sapiens proteomes. Int J Med Med Sci 2009; 1: 383–387.

  90. 90

    Natale C, Giannini T, Lucchese A, Kanduc D. Computer-assisted analysis of molecular mimicry between human papillomavirus 16 E7 oncoprotein and human protein sequences. Immunol Cell Biol 2000; 78: 580–585.

  91. 91

    Klumb EM, Pinto AC, Jesus GR, Araujo M, Jascone L, Gayer CR et al. Are women with lupus at higher risk of HPV infection? Lupus 2010; 19: 1485–1491.

  92. 92

    Lyrio LDC, Grassi MFR, Santana IU, Olavarria VG, Gomes A, do N, CostaPinto L et al. Prevalence of cervical human papillomavirus infection in women with systemic lupus erythematosus. Rheumatol Int 2013; 33: 335–340.

  93. 93

    Segal Y, Dahan S, Calabrò M, Kanduc D, Shoenfeld Y. HPV and systemic lupus erythematosus: a mosaic of potential crossreactions. Immunol Res 2017; 65: 564–571.

  94. 94

    Segal Y, Calabrò M, Kanduc D, Shoenfeld Y. Human papilloma virus and lupus: the virus, the vaccine and the disease. Curr Opin Rheumatol 2017; 29: 331–342.

  95. 95

    Gatto M, Agmon-Levin N, Soriano A, Manna R, Maoz-Segal R, Kivity S et al. Human papillomavirus vaccine and systemic lupus erythematosus. Clin Rheumatol 2013; 32: 1301–1307.

  96. 96

    Soldevilla HF, Briones SFR, Navarra SV. Systemic lupus erythematosus following HPV immunization or infection? Lupus 2012; 21: 158–161.

  97. 97

    Ito H, Noda K, Hirai K, Ukichi T, Furuya K, Kurosaka D. A case of systemic lupus erythematosus (SLE) following human papillomavirus (HPV) vaccination. Nihon Rinsho Meneki Gakkai Kaishi 2016; 39: 145–149.

  98. 98

    Wang B, Shao X, Wang D, Xu D, Zhang J-A. Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: a systematic review and meta-analysis. Autoimmun Rev 2017; 16: 756–765.

  99. 99

    Geier DA, Geier MR. Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case–control assessment of the vaccine adverse event reporting system (VAERS) database. Immunol Res 2016; 65: 46–54.

  100. 100

    Grubb BP, Kanjwal Y, Kosinski DJ. The postural tachycardia syndrome: a concise guide to diagnosis and management. J Cardiovasc Electrophysiol 2006; 17: 108–112.

  101. 101

    Haensch C-A, Tosch M, Katona I, Weis J, Isenmann S. Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome. Muscle Nerve 2014; 50: 956–961.

  102. 102

    Low PA, Sandroni P, Joyner M, Shen W-K. Postural Tachycardia Syndrome (POTS). J Cardiovasc Electrophysiol 2009; 20: 352–358.

  103. 103

    Martínez-Lavín M. Hypothesis: human papillomavirus vaccination syndrome—small fiber neuropathy and dysautonomia could be its underlying pathogenesis. Clin Rheumatol 2015; 34: 1165–1169.

  104. 104

    Üçeyler N. Small fiber pathology—a culprit for many painful disorders? Pain 2016; 157 (Suppl 1): S60–S66.

  105. 105

    Dahan S, Tomljenovic L, Shoenfeld Y. Postural orthostatic tachycardia syndrome (POTS)—a novel member of the autoimmune family. Lupus 2016; 25: 339–342.

  106. 106

    Wang X-L, Chai Q, Charlesworth MC, Figueroa JJ, Low P, Shen W-K et al. Autoimmunoreactive IgGs from patients with postural orthostatic tachycardia syndrome. Proteomics Clin Appl 2012; 6: 615–625.

  107. 107

    Blitshteyn S. Postural tachycardia syndrome after vaccination with Gardasil. Eur J Neurol 2010; 17: e52.

  108. 108

    Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol 2014; 21: 135–139.

  109. 109

    Tomljenovic L, Colafrancesco S, Perricone C, Shoenfeld Y. Postural orthostatic tachycardia with chronic fatigue after HPV vaccination as part of the ‘autoimmune/auto-inflammatory syndrome induced by adjuvants’: case report and literature review. J Investig Med High Impact Case Rep 2014; 2: 1–8.

  110. 110

    Brinth LS, Pors K, Theibel AC, Mehlsen J. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus. Vaccine 2015; 33: 2602–2605.

  111. 111

    Hendrickson JE, Tormey CA. Human papilloma virus vaccination and dysautonomia: considerations for autoantibody evaluation and HLA typing. Vaccine 2016; 34: 4468.

  112. 112

    Brinth L, Theibel AC, Pors K, Mehlsen J. Suspected side effects to the quadrivalent human papilloma vaccine. Dan Med J 2015; 62: A5064.

  113. 113

    Palmieri B, Poddighe D, Vadalà M, Laurino C, Carnovale C, Clementi E. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res 2017; 65: 106–116.

  114. 114

    Kafaie J, Kim M, Krause E. Small fiber neuropathy following vaccination. J Clin Neuromuscul Dis 2016; 18: 37–40.

  115. 115

    Chandler RE, Juhlin K, Fransson J, Caster O, Edwards IR, Norén GN. Current safety concerns with human papillomavirus vaccine: a cluster analysis of reports in VigiBase®. Drug Saf 2017; 40: 81–90.

  116. 116

    Li H, Yu X, Liles C, Khan M, Vanderlinde-Wood M, Galloway A et al. Autoimmune basis for postural tachycardia syndrome. J Am Heart Assoc 2014; 3: e000755.

  117. 117

    Li Y, Heuser JS, Cunningham LC, Kosanke SD, Cunningham MW. Mimicry and antibody-mediated cell signaling in autoimmune myocarditis. J Immunol 2006; 177: 8234–8240.

  118. 118

    Kanduc D. Potential cross-reactivity between HPV16 L1 protein and sudden death-associated antigens. J Exp Ther Oncol 2011; 9: 159–165.

  119. 119

    Versini M, Jeandel P-Y, Bashi T, Bizzaro G, Blank M, Shoenfeld Y. Unraveling the hygiene hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications. BMC Med 2015; 13: 81.

  120. 120

    Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80: 695–705.

  121. 121

    Kanduc D, Shoenfeld Y. From HBV to HPV: designing vaccines for extensive and intensive vaccination campaigns worldwide. Autoimmun Rev 2016; 15: 1054–1061.

Download references

Author information


  1. Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, 52621, Israel

    • Yahel Segal
    •  & Yehuda Shoenfeld
  2. Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel

    • Yehuda Shoenfeld


  1. Search for Yahel Segal in:

  2. Search for Yehuda Shoenfeld in:

Conflict of interest

Prof. Yehuda Shoenfeld has served as an expert witness in cases involving adverse vaccine reaction in the no-fault US National Vaccine Injury Compensation Program.

Corresponding author

Correspondence to Yehuda Shoenfeld.

About this article

Publication history