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.