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

Rotem Inbar, Ronen Weiss, Lucija Tomljenovic, Maria Teresa Arango, Yael Deri, Christopher A. Shaw, Joab Chapman, Miri Blank, Yehuda Shoenfeld

Resultado de la investigación: Contribución a RevistaArtículo

13 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)136-149
Número de páginas14
PublicaciónImmunologic Research
Volumen65
N.º1
DOI
EstadoPublished - feb 1 2017

Huella dactilar

Papillomavirus Vaccines
Aluminum
Pertussis Toxin
Vaccines
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
Placebos
Aluminum Hydroxide
Poisons
Locomotion
Hippocampus

All Science Journal Classification (ASJC) codes

  • Immunology

Citar esto

Inbar, Rotem ; Weiss, Ronen ; Tomljenovic, Lucija ; Arango, Maria Teresa ; Deri, Yael ; Shaw, Christopher A. ; Chapman, Joab ; Blank, Miri ; Shoenfeld, Yehuda. / Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. En: Immunologic Research. 2017 ; Vol. 65, N.º 1. pp. 136-149.
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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.",
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Inbar, R, Weiss, R, Tomljenovic, L, Arango, MT, Deri, Y, Shaw, CA, Chapman, J, Blank, M & Shoenfeld, Y 2017, 'Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil', Immunologic Research, vol. 65, n.º 1, pp. 136-149. https://doi.org/10.1007/s12026-016-8826-6

Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. / Inbar, Rotem; Weiss, Ronen; Tomljenovic, Lucija; Arango, Maria Teresa; Deri, Yael; Shaw, Christopher A.; Chapman, Joab; Blank, Miri; Shoenfeld, Yehuda.

En: Immunologic Research, Vol. 65, N.º 1, 01.02.2017, p. 136-149.

Resultado de la investigación: Contribución a RevistaArtículo

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T1 - Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil

AU - Inbar, Rotem

AU - Weiss, Ronen

AU - Tomljenovic, Lucija

AU - Arango, Maria Teresa

AU - Deri, Yael

AU - Shaw, Christopher A.

AU - Chapman, Joab

AU - Blank, Miri

AU - Shoenfeld, Yehuda

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