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

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.

Distinctive cellular response to aluminum based adjuvants

“…Behavioral abnormalities were detected in mice exposed to clinically relevant doses of aluminum hydroxide or the human papillomavirus vaccine, Gardasil, which J o u r n a l P r e -p r o o f contains aluminum as an adjuvant (Inbar et al, 2016). Altered behavior and an increase in microglial density was observed in mice exposed to Alhydrogel (Crepeaux et al, 2017).…”

The knowledge and attitudes of students about human papillomavirus and HPV vaccine

“…Primenu HPV vakcine i njen značaj u prevenciji karcinoma grlića materice potvrdile su neke studije [26,27], dok ima i onih koje navode ograničen doprinos i negativne efekte vakcinacije. O stvarnim efektima vakcine može se govoriti tek tada kad se dokaže da vakcina prevenira klinički manifestnu bolest, a ne samo dispaziju [28,29].…”

“…RESEARCH RESULTS: The average age of health workers was 43.70 ± 11.90 years, while the average age of educational workers was 42. 29…”

Vaccination and Autoimmune Phenomena

“…Similarly, exposure to HBV vaccine has been found to accelerate disease progression in a murine model of lupus (8). A number of published papers has also expressed concern regarding the biopersistence and possible neutotoxicity of aluminium-based adjuvants, with some apparent support from animal models (9,10,11). The question of relevance of these examples to adjuvant/vaccine safety assessment is, however, not to be taken lightly.…”