Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin

Abstract

Vaccination is the most powerful way to prevent human beings from contracting infectious diseases including viruses. In the case of the human papillomavirus (HPV) vaccine, an unexpectedly novel disease entity, HPV vaccination associated neuro-immunopathetic syndrome (HANS), has been reported and remains to be carefully verified. To elucidate the mechanism of HANS, we applied a strategy similar to the active experimental autoimmune encephalitis (EAE) model - one of the most popular animal models used to induce maximum immunological change in the central nervous system. Surprisingly, mice vaccinated with pertussis toxin showed neurological phenotypes that include low responsiveness of the tail reflex and locomotive mobility. Pathological analyses revealed the damage to the hypothalamus and circumventricular regions around the third ventricle, and these regions contained apoptotic vascular endothelial cells. These data suggested that HPV-vaccinated donners that are susceptible to the HPV vaccine might develop HANS under certain environmental factors. These results will give us the new insight into the murine pathological model of HANS and help us to find a way to treat of patients suffering from HANS.

miR-451a levels rather than human papillomavirus vaccine administration is associated with the severity of murine experimental autoimmune encephalomyelitis

“…Previously, Aratani S et al reported that HPV vaccines induce murine EAE-like disease, suggesting that the HPV vaccine adjuvant is the cause of mouse EAE exacerbation 13 . Although HPV vaccines induce pro-inflammatory cytokine expression as described above, the administration of Gardasil and Cervarix did not affect murine EAE clinical scores (Fig.…”

“…Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disorder affecting the CNS such as ADEM, and it represents an animal model of multiple sclerosis 12 . There was a report that HPV vaccines induce EAE-like symptoms in mice 13 ; however, the paper was retracted because of an inappropriate experimental approach 14 . Cervarix, an HPV vaccine, contains the AS04 adjuvant, which includes monophosphoryl lipid A (MPLA) and aluminum adjuvants.…”

Suspected Adverse Effects After Human Papillomavirus Vaccination: A Temporal Relationship Between Vaccine Administration and the Appearance of Symptoms in Japan

“…Further large-scale studies are needed to elucidate the pathogenesis of this unusual phenomenon. To this end, a murine pathological model was recently established by combined administration of HPV vaccine and pertussis toxin [ 40 ], which might be helpful for investigating immune-related pathological conditions in this post-vaccinated disorder.…”

Vaccination and Autoimmune Phenomena

“…For instance, mice have been reported to have developed autoantibodies after intraperitoenal injection of hydrocarbon oil-based adjuvants (6). In another murine model, concomitant exposure to HPV vaccine and pertussis toxin has reportedly resulted in hypothalamic destruction (7). Similarly, exposure to HBV vaccine has been found to accelerate disease progression in a murine model of lupus (8).…”