The present invention relates to the field of vaccination or immunization, in particular therapeutic vaccination, and diagnosis. Pharmaceutical compositions and kits capable of eliciting a protective immune response against polyoma virus JC (JCV) are disclosed, which may be used e.g., for therapy or for prevention of progressive multifocal leukoencephalopathy (PML) and/or progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS). Individuals in danger of such PML or PML-IRIS may, e.g., be immuno-compromised or immunosuppressed patients or patients having an autoimmune disease eligible for immunosuppressive treatment. The invention also relates to compositions comprising at least one CD4+ epitope of a JCV protein and to therapeutic, prophylactic and diagnostic uses thereof.