Skip to main content

Advertisement

SpringerLink
Log in

Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil

  • Environment and Autoimmunity
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil + pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5 months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, p = 0.009; Gardasil, p = 0.025; Gardasil + Pt, p = 0.005). The increase in floating time was already highly significant at 4.5 months of age for the Gardasil and Gardasil + Pt group (p ≤ 0.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil + Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

Al:

Aluminum

ASIA:

Autoimmune/autoinflammatory syndrome induced by adjuvants

β2-GPI:

β2-Glycoprotein I

FST:

Forced swimming test

HPV:

Human papilloma virus

Pt:

Pertussis toxin

U. S FDA:

United States Food and Drug Administration

References

  1. Marra F, et al. A meta-analysis of intradermal versus intramuscular influenza vaccines: immunogenicity and adverse events. Influenza Other Respir Viruses. 2013;7(4):584–603. doi:10.1111/irv.12000.

    Article  PubMed  Google Scholar 

  2. Perricone C, et al. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun. 2013;47:1–16. doi:10.1016/j.jaut.2013.10.004.

    Article  CAS  PubMed  Google Scholar 

  3. Tomljenovic L, Shaw CA. No autoimmune safety signal after vaccination with quadrivalent HPV vaccine Gardasil? J Intern Med. 2012;272(5):514–5. doi:10.1111/j.1365-2796.2012.02551.x.

    Article  CAS  PubMed  Google Scholar 

  4. Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol. 2014;21(1):135–9. doi:10.1111/ene.12272.

    Article  CAS  PubMed  Google Scholar 

  5. Poser CM, Behan PO. Late onset of Guillain-Barre syndrome. J Neuroimmunol. 1982;3(1):27–41.

    Article  CAS  PubMed  Google Scholar 

  6. Ryan AM, et al. Atypical presentation of macrophagic myofasciitis 10 years post vaccination. Neuromuscul Disord. 2006;16(12):867–9. doi:10.1016/j.nmd.2006.07.017.

    Article  PubMed  Google Scholar 

  7. Exley C. Aluminium-based adjuvants should not be used as placebos in clinical trials. Vaccine. 2011;29(50):9289. doi:10.1016/j.vaccine.2011.08.062.

    Article  PubMed  Google Scholar 

  8. Lujan L, et al. Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep. Immunol Res. 2013;56(2–3):317–24. doi:10.1007/s12026-013-8404-0.

    Article  CAS  PubMed  Google Scholar 

  9. Couette M, et al. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction. J Inorg Biochem. 2009;103(11):1571–8. doi:10.1016/j.jinorgbio.2009.08.005.

    Article  CAS  PubMed  Google Scholar 

  10. Gherardi RK, et al. Biopersistence and brain translocation of aluminum adjuvants of vaccines. Front Neurol. 2015;6:4. doi:10.3389/fneur.2015.00004.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rigolet M, et al. Clinical features in patients with long-lasting macrophagic myofasciitis. Front Neurol. 2014;5:230. doi:10.3389/fneur.2014.00230.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Marrack P, et al. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol. 2009;9(4):287–93. doi:10.1038/nri2510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shaw CA, Petrik MS. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorg Biochem. 2009;103(11):1555–62. doi:10.1016/j.jinorgbio.2009.05.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li X, et al. Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains. Nanomedicine. 2009;5(4):473–9.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu Y, et al. Immunotoxicity of aluminum. Chemosphere. 2014;104:1–6. doi:10.1016/j.chemosphere.2013.10.052.

    Article  PubMed  Google Scholar 

  16. Chen L, et al. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol. 2008;3(4):286–95. doi:10.1007/s11481-008-9131-5.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Eldred BE, et al. Vaccine components and constituents: responding to consumer concerns. Med J Aust. 2006;184(4):170–5.

    PubMed  Google Scholar 

  18. Shoenfeld Y, et al. Vaccination as an additional player in the mosaic of autoimmunity. Clin Exp Rheumatol. 2000;18(2):181–4.

    CAS  PubMed  Google Scholar 

  19. Shoenfeld Y. Infections, vaccines and autoimmunity. Lupus. 2009;18(13):1127–8. doi:10.1177/0961203309351081.

    Article  CAS  PubMed  Google Scholar 

  20. Tomljenovic L, Shaw CA. Human papillomavirus (HPV) vaccine policy and evidence-based medicine: Are they at odds? Ann Med. 2013;45(2):182–93. doi:10.3109/07853890.2011.645353.

    Article  PubMed  Google Scholar 

  21. Garland SM, et al. (FUTURE) I Investigators) Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928–43. doi:10.1056/NEJMoa061760.

    Article  CAS  PubMed  Google Scholar 

  22. Munoz N, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. Lancet. 2009;373(9679):1949–57. doi:10.1016/S0140-6736(09)60691-7.

    Article  CAS  PubMed  Google Scholar 

  23. Can A, et al. The mouse forced swim test. J Vis Exp. 2012;59:e3638. doi:10.3791/3638.

    Google Scholar 

  24. Tordera RM, et al. Enhanced anxiety, depressive-like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1). Eur J Neurosci. 2007;25:281–90.

    Article  CAS  PubMed  Google Scholar 

  25. Katzav A, et al. Hyperactivity in a mouse model of the antiphospholipid syndrome. Lupus. 2001;10:496–9.

    Article  CAS  PubMed  Google Scholar 

  26. Brown JA, et al. Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Human Mol Genet. 2010;19(22):4515–28.

    Article  CAS  Google Scholar 

  27. Harper DM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367(9518):1247–55. doi:10.1016/S0140-6736(06)68439-0.

    Article  CAS  PubMed  Google Scholar 

  28. Villa LL, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005;6(5):271–8. doi:10.1016/S1470-2045(05)70101-7.

    Article  PubMed  Google Scholar 

  29. Mao C, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006;107(1):18–27. doi:10.1097/01.AOG.0000192397.41191.fb.

    Article  PubMed  Google Scholar 

  30. Group TFIS. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356(19):1915–27. doi:10.1056/NEJMoa061741.

    Article  Google Scholar 

  31. Verstraeten T, et al. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008;26(51):6630–8. doi:10.1016/j.vaccine.2008.09.049.

    Article  CAS  PubMed  Google Scholar 

  32. Guimaraes LE, et al. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209. doi:10.1016/j.phrs.2015.08.003.

    Article  CAS  PubMed  Google Scholar 

  33. Shaw CA, et al. Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy? Immunotherapy. 2014;6(10):1055–71. doi:10.2217/imt.14.81.

    Article  CAS  PubMed  Google Scholar 

  34. Exley C. Aluminium adjuvants and adverse events in sub-cutaneous allergy immunotherapy. Allergy Asthma Clin Immunol. 2014;10(1):4. doi:10.1186/1710-1492-10-4.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Passeri E, et al. Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF). J Inorg Biochem. 2011;105(11):1457–63. doi:10.1016/j.jinorgbio.2011.08.006.

    Article  CAS  PubMed  Google Scholar 

  36. Zivkovic I, et al. Induction of decreased fecundity by tetanus toxoid hyper-immunization in C57BL/6 mice depends on the applied adjuvant. Innate Immun. 2012;18(2):333–42. doi:10.1177/1753425911407361.

    Article  CAS  PubMed  Google Scholar 

  37. Agmon-Levin N, et al. Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. J Autoimmun. 2014;54:21–32. doi:10.1016/j.jaut.2014.06.006.

    Article  CAS  PubMed  Google Scholar 

  38. Exley C, Birchall JD. The cellular toxicity of aluminium. J Theor Biol. 1992;159(1):83–98.

    Article  CAS  PubMed  Google Scholar 

  39. Shaw CA, Tomljenovic L. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol Res. 2013;56(2–3):304–16. doi:10.1007/s12026-013-8403-1.

    Article  CAS  PubMed  Google Scholar 

  40. Offit PA, Jew RK. Addressing parents’ concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics. 2003;112(6 Pt 1):1394–7.

    Article  PubMed  Google Scholar 

  41. Khan Z, et al. Slow CCL2-dependent translocation of biopersistent particles from muscle to brain. BMC Med. 2013;11:99. doi:10.1186/1741-7015-11-99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gherardi RK, et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain. 2001;124(Pt 9):1821–31.

    Article  CAS  PubMed  Google Scholar 

  43. Lee SH. Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil® vaccination—a case report. Adv Biosci Biotech. 2012;3:1214–24.

    Article  Google Scholar 

  44. Walton JR. A longitudinal study of rats chronically exposed to aluminum at human dietary levels. Neurosci Lett. 2007;412(1):29–33. doi:10.1016/j.neulet.2006.08.093.

    Article  CAS  PubMed  Google Scholar 

  45. Xiu C, et al. Aluminum chloride- and norepinephrine-induced immunotoxicity on splenic lymphocytes by activating beta-AR/cAMP/PKA/NF-kappaB signal pathway in rats. Biol Trace Elem Res. 2014;162(1–3):168–74. doi:10.1007/s12011-014-0149-7.

    Article  CAS  PubMed  Google Scholar 

  46. Caulfield MJ, et al. Effect of alternative aluminum adjuvants on the absorption and immunogenicity of HPV16 L1 VLPs in mice. Human Vaccin. 2007;3(4):139–45.

    Article  Google Scholar 

  47. FDA. Food and Drug Administration. Inside clinical trials: testing medical products in people. (2009).

  48. Kanduc D. Potential cross-reactivity between HPV16 L1 protein and sudden death-associated antigens. J Exp Ther Oncol. 2011;9(2):159–65.

    CAS  PubMed  Google Scholar 

  49. Yonee C, et al. Association of acute cerebellar ataxia and human papilloma virus vaccination: a case report. Neuropediatrics. 2013;44(5):265–7. doi:10.1055/s-0033-1333873.

    Article  PubMed  Google Scholar 

  50. Kanduc D. Quantifying the possible cross-reactivity risk of an HPV16 vaccine. J Exp Ther Oncol. 2009;8(1):65–76.

    CAS  PubMed  Google Scholar 

  51. van Bogaert L. Are the currently existing anti-human papillomavirus vaccines appropriate for the developing world? Ann Med Health Sci Res. 2013;3(3):306–12. doi:10.4103/2141-9248.117924.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Mendoza Plasencia Z, et al. Acute disseminated encephalomyelitis with tumefactive lesions after vaccination against human papillomavirus. Neurologia. 2010;25(1):58–9.

    Article  CAS  PubMed  Google Scholar 

  53. Wildemann B, et al. Acute disseminated encephalomyelitis following vaccination against human papilloma virus. Neurology. 2009;72(24):2132–3. doi:10.1212/WNL.0b013e3181aa53bb.

    Article  CAS  PubMed  Google Scholar 

  54. Sutton I, et al. CNS demyelination and quadrivalent HPV vaccination. Mult Scler. 2009;15(1):116–9.

    Article  CAS  PubMed  Google Scholar 

  55. Chang J, et al. Demyelinating disease and polyvalent human papilloma virus vaccination. J Neurol Neurosurg Psychiatry. 2011;82(11):1296–8. doi:10.1136/jnnp.2010.214924.

    Article  PubMed  Google Scholar 

  56. McCarthy JE, Filiano J. Opsoclonus Myoclonus after human papilloma virus vaccine in a pediatric patient. Parkinsonism Relat Disord. 2009;15(10):792–4. doi:10.1016/j.parkreldis.2009.04.002.

    Article  PubMed  Google Scholar 

  57. Menge T, et al. Neuromyelitis optica following human papillomavirus vaccination. Neurology. 2012;79(3):285–7. doi:10.1212/WNL.0b013e31825fdead.

    Article  PubMed  Google Scholar 

  58. DiMario FJ Jr, et al. A 16-year-old girl with bilateral visual loss and left hemiparesis following an immunization against human papilloma virus. J Child Neurol. 2010;25(3):321–7. doi:10.1177/0883073809349322.

    Article  PubMed  Google Scholar 

  59. Alvarez-Soria MJ, et al. Trastornos neurológicos desmielinizantes y vacunación del papilomavirus humano. Rev Neurol. 2011;52(8):472–6.

    PubMed  Google Scholar 

  60. Zhu YZ, et al. impact of aluminum exposure on the immune system: a mini review. Environ Toxicol Pharmacol. 2013;35(1):82–7. doi:10.1016/j.etap.2012.11.009.

    Article  CAS  PubMed  Google Scholar 

  61. Debeer P, et al. Brachial plexus neuritis following HPV vaccination. Vaccine. 2008;26(35):4417–9. doi:10.1016/j.vaccine.2008.06.074.

    Article  PubMed  Google Scholar 

  62. Brinth LS, et al. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus. Vaccine. 2015;33(22):2602–5. doi:10.1016/j.vaccine.2015.03.098.

    Article  PubMed  Google Scholar 

  63. Kinoshita T, et al. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53(19):2185–200.

    Article  PubMed  Google Scholar 

  64. Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol. 2014;21:135–9. doi:10.1111/ene.12272.

    Article  CAS  PubMed  Google Scholar 

  65. Richards S, et al. Complex regional pain syndrome following immunisation. Arch Dis Child. 2012;97(10):913–5. doi:10.1136/archdischild-2011-301307.

    Article  PubMed  Google Scholar 

  66. Tomljenovic L, et al. Postural orthostatic tachycardia with chronic fatigue after HPV vaccination as part of the “autoimmune/autoinflammatory syndrome induced by adjuvants”: case report and literature review. J Investig Med High Impact Case Rep. 2014;. doi:10.1177/2324709614527812.

    PubMed  PubMed Central  Google Scholar 

  67. Martinez-Lavin M. Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheumatol. 2014;20(7):392–3. doi:10.1097/RHU.0000000000000165.

    PubMed  Google Scholar 

  68. Cerami C, et al. Autoimmune neuromyotonia following human papilloma virus vaccination. Muscle Nerve. 2013;47(3):466–7. doi:10.1002/mus.23648.

    Article  PubMed  Google Scholar 

  69. Colafrancesco S, et al. HPV vaccines and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Am J Reprod Immunol. 2013;70(4):309–16.

    Article  CAS  PubMed  Google Scholar 

  70. Little DT, Grenville Ward HR. Adolescent premature ovarian insufficiency following human papillomavirus vaccination: a case series seen in general practice. J Investig Med High Impact Case Rep. 2014;. doi:10.1177/2324709614556129.

    PubMed  PubMed Central  Google Scholar 

  71. Melo Gomes S, et al. Vasculitis following HPV immunization. Rheumatology (Oxford). 2013;52(3):581–2. doi:10.1093/rheumatology/kes168.

    Article  Google Scholar 

  72. Pugnet G, et al. Immune thrombocytopenic purpura following human papillomavirus vaccination. Vaccine. 2009;27(28):3690. doi:10.1016/j.vaccine.2009.04.004.

    Article  PubMed  Google Scholar 

  73. Della Corte C, et al. Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl. Vaccine. 2011;29(29):4654–6. doi:10.1016/j.vaccine.2011.05.002.

    Article  PubMed  Google Scholar 

  74. Das A, et al. Pancreatitis following human papillomavirus vaccination. Med J Aust. 2008;189(3):178.

    PubMed  Google Scholar 

  75. Soldevilla HF, et al. Systemic lupus erythematosus following HPV immunization or infection? Lupus. 2012;21(2):158–61. doi:10.1177/0961203311429556.

    Article  CAS  PubMed  Google Scholar 

  76. Gatto M, et al. Human papillomavirus vaccine and systemic lupus erythematosus. Clin Rheumatol. 2013;32(9):1301–7. doi:10.1007/s10067-013-2266-7.

    Article  PubMed  Google Scholar 

  77. Anaya JM, et al. Autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination in Colombians: a call for personalised medicine. Clin Exp Rheumatol. 2015;33(4):545–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, 52621, Israel, Israel

    Rotem Inbar, Lucija Tomljenovic, Maria-Teresa Arango, Yael Deri, Joab Chapman, Miri Blank & Yehuda Shoenfeld

  2. Department of Obstetrics and Gynecology, Sheba Medical Center, 52621, Tel Hashomer, Israel

    Rotem Inbar

  3. Sagol School of Neuroscience, Tel Aviv University, 69978, Ramat Aviv, Israel

    Ronen Weiss

  4. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Ramat Aviv, Israel

    Ronen Weiss

  5. Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada

    Lucija Tomljenovic & Christopher A. Shaw

  6. Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogota, 111221, Colombia

    Maria-Teresa Arango

  7. Department of Neurology and Sagol Neuroscience Center, The Sheba Medical Center, 52621, Tel Hashomer, Israel

    Joab Chapman

  8. Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, 69978, Ramat Aviv, Israel

    Yehuda Shoenfeld

Authors
  1. Rotem Inbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronen Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucija Tomljenovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria-Teresa Arango
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yael Deri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher A. Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joab Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miri Blank
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yehuda Shoenfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yehuda Shoenfeld.

Ethics declarations

Conflict of interest

Yehuda Shoenfeld has acted as a consultant for the no-fault US National Vaccine Injury Compensation Program. L.T. has served as an expert witness in cases involving adverse reactions following qHPV vaccine administration. The other co-authors declare no competing interests.

Funding

This work was supported by the grants from the Dwoskin Foundation Ltd.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inbar, R., Weiss, R., Tomljenovic, L. et al. Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. Immunol Res 65, 136–149 (2017). https://doi.org/10.1007/s12026-016-8826-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8826-6

Keywords

Search

Navigation