Vaccine for the Treatment of Prion Diseases

Antibody-based immunotherapy represents an important approach for treating prion diseases, providing antibodies to the cellular prion protein PrP can antagonize the conversion and deposition of PrP in in vitro assays and in laboratory animals. However, induction of protective anti-prion immune responses in wild-type animals is difficult because of host tolerance to the endogenous PrP - (Heppner and Aguzzi, 20(M). 

In order to develop an anti-prion vaccine, a novel DNA fusion vaccine composed of mouse PrP and immune stimulatory helper T-cell epitopes of the tetanus toxin has been developed (Nitschke et al., 2007). This approach provokes a strong PrP -specific humoral and cellular immune response in PrP null mice, but only low antibody titers are found in vaccinated wild-type mice. Furthermore, prime-boost immunization with the DNA vaccine and recombinant PrP protein increased antibody titres in PrP null mice, but failed to protect wild-type mice from mouse scrapie (Nitschke et al., 2007). 

Recent studies indicate that it is possible to overcome tolerance to Prl and induce immune responses to bacterially expressed, recombinant PrP. Nevertheless, in vivo deleterious side effects of injected anti-PrP antibodies have been reported, mainly due to their Fc fragments and divalence. Removal of Fc fragments has no effect on prion replication inhibiting activity of Fabs in infected neuronal cells (Alexandrenne et al., 2009). It is suggested that for immunotherapy of prion 

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