Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin
Authors: Toshihiro Nakajima
Yoshiyuki Kuroiwa
Kusuki Nishioka
Chie Usui
Hidetoshi Fujita
Shumpei Yokota
Satoko Aratani
Ikuro Nakamura
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Vaccination; infectious diseases; human papillomavirus (HPV); neuro-immunopathetic syndrome (HANS); mechanism
Affiliations: Institute of Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan., Department of Future Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan., Physician, Student and Researcher Support Center, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan., Department of Neurology and Stroke Center, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan., Department of Psychiatry, Juntendo University Nerima Hospital, Nerima-ku, Tokyo, Japan., Japan Medical Research Foundation, Chiyoda-ku, Tokyo, Japan., Integrated Gene Editing Section (iGES), Tokyo Medical University Hospital, Shinjuku-ku, Tokyo, Japan.

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. 

Retracted: Yes

PubPeer comments:
 Retracted: https: www.nature.com articles srep46971  The Publisher is retracting this Article because the experimental approach does not support the objectives of the study. The study was designed to elucidate the maximum implication of human papilloma virus (HPV) vaccine (Gardasil) in the central nervous system. However, the co-administration of pertussis toxin with high-levels of HPV vaccine is not an appropriate approach to determine neurological damage from HPV vaccine alone. The Authors do not agree with the retraction. More details: http: www.sciencemag.org news 2018 05 journal-retracts-paper-claiming-neurological-damage-hpv-vaccine  The paper, by a group led by Toshihiro Nakajima of Tokyo Medical University, was published online 11 November 2016. It describes impaired mobility and brain damage in mice given an enormous dose of HPV vaccine along with a toxin that makes the blood-brain barrier leaky. Shortly after the paper appeared, two groups separately wrote to Scientific Reports and its publisher, the Nature Publishing Group (NPG), pointing out problems with the experimental setup, the use of a dose proportionally far larger than what is normally given, the use of the toxin, and inconsistencies between the data presented and the descriptions of results, among other issues. At the time, Nakajima defended the paper in an email to Science, claiming the experimental strategy was similar to those commonly used in other mouse studies. He also wrote that the group was preparing a detailed response to the criticisms. , 
 This paper has been retracted for problems in the experimental setup but it is also worth pointing out a possible duplication in Figure 2C. These panels show  (c) KB staining of serial coronal sections  of the forebrain from mice treated with vehicle (upper) and with vaccine and Ptx (lower)  * Red boxes draw attention to a panel in the vehicle row that looks very similar to a panel in the vaccine PTX row. ![file] ,