title: BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.
abstract: There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Yong
authors.forename: Goran
authors.initials: G
authors.lastname: Lacan
authors.forename: Hoa
authors.initials: H
authors.lastname: Dang
authors.forename: Terry
authors.initials: T
authors.lastname: Hsieh
authors.forename: Blake
authors.initials: B
authors.lastname: Middleton
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Jide
authors.initials: J
authors.lastname: Tian
authors.forename: William P
authors.initials: WP
authors.lastname: Melega
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum; D004195:Disease Models, Animal; D004298:Dopamine; D051379:Mice; D018696:Neuroprotective Agents; D010300:Parkinson Disease / Q000628:therapy*; D013378:Substantia Nigra; D014446:Tyrosine 3-Monooxygenase / Q000627:therapeutic use; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine