Authors: Inbar R1, Weiss R2, Tomljenovic L3, Arango MT4, Deri Y5, Shaw CA6, Chapman J7, Blank M5, Shoenfeld Y8
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 young 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 six months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison to 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 three 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 nor in rotarod performance, both of which measure locomotor activity. Since rotarod also measures muscular strength, collectively these results indicate that differences observed in the FST were not due to locomotor dysfunction, but likely due to depression. Additionally, at three months of age, compared to control mice, Al-injected mice showed a significantly decreased preference for the new arm in the Y maze test (p=0.03), indicating short-term memory impairment. 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 compared to the control. 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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