Immunization with Recombinant Prion Protein Leads to Partial Protection in a Murine Model of TSEs through a Novel Mechanism

Abstract

Transmissible spongiform encephalopathies are neurodegenerative diseases, which despite fervent research remain incurable. Immunization approaches have shown great potential at providing protection, however tolerance effects hamper active immunization protocols. In this study we evaluated the antigenic potential of various forms of recombinant murine prion protein and estimated their protective efficacy in a mouse model of prion diseases. One of the forms tested provided a significant elongation of survival interval. The elongation was mediated via an acute depletion of mature follicular dendritic cells, which are associated with propagation of the prion infectious agent in the periphery and in part to the development of humoral immunity against prion protein. This unprecedented result could offer new strategies for protection against transmissible encephalopathies as well as other diseases associated with follicular dendritic cells.

Prion Protein-Specific Antibodies-Development, Modes of Action and Therapeutics Application

“…The evaluation of essential protective immune response properties in different mouse models revealed the importance of an antigen to provoke antibodies recognizing cell-surface PrP C [ 66 ]. This finding was confirmed in the recent study identifying compounds with the best immunogenic potential, in which the protection model was further associated with depletion of mature follicular dendritic cells, which spread peripheral prion infection [ 67 ]. Encouraging results in the generation of host antibodies towards PrP C were obtained using PrP monomer peptides, multiple antigenic peptides, full PrPs, proteins resembling PrP epitopes or PrP dimers as the antigen of choice, administrated through various vector-, protein-, virus- or cell-carriers [ 49 , 50 , 74 ].…”

“…Such localization favors the accessibility of both targets to the antibodies and warrants the maintenance of the stable antibody-target complexes. The ability of an antibody to recognize native PrP C molecules expressed on the plasma membrane may discriminate protective vs. non-protective immune responses [ 66 , 67 , 68 ]. In many cases, antibodies that have shown significant clearing capacities were internalized into the cells [ 28 , 52 , 69 , 70 ] suggesting their potential to exhibit additional positive effects also along the endocytic pathway.…”

The Case for Involvement of Spiroplasma in the Pathogenesis of Transmissible Spongiform Encephalopathies

“…The development of a vaccine to control TSE based on the prion has only been partially successful (98). The problem in following this line of research is the danger of ending up with an autoreactive PrP antibody, which would be difficult to implement because of potential side effects (99).…”

Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

“…[12][13][14][15][16][17][18] Numerous studies have shown the benefits of immunization to abrogate infectivity, reduce PrP Sc loads within relevant tissue, increase survival time, and provide partial protection following infection. [19][20][21][22][23][24][25][26][27][28][29] Further, the paradigms of vaccine success are shifting such that reduced shedding, rather than outright prevention of infection, may be a relevant and achievable measure of vaccine efficacy.…”