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<p>Prion diseases, such as chronic wasting disease (CWD), are incurable, fatal neurodegenerative disorders. We have developed a recombinant dimeric deer prion protein (Ddi) vaccine against CWD that has shown promising immune responses when injected subcutaneously (s.c). While s.c injection is suitable for controlled conditions, oral administration is practical in wildlife. Herein, we have developed an oral vaccine utilizing poly lactic co-glycolic acid (PLGA) nanoparticles, co-encapsulating Ddi and oligodeoxynucleotide adjuvant (CpG) using double emulsion-solvent evaporation technique. Our results showed production of spherical PLGA nanoparticles with size of ~ 200–300&#xa0;nm, an acceptable surface charge (− 14.2 ± 5.73 mV), and an encapsulation efficiency of approximately 70 and 30%, for Ddi and CpG, respectively. We administered the developed vaccine to FVB mice orally and subcutaneously, followed by ELISA assays of the sera and feces. Mice receiving the vaccine subcutaneously exhibited high antibody reactivities to the used antigen in their sera (100% positivity), with no detectable positive reactivity in their feces. However, those receiving the oral vaccine showed 60 and 80% positivity in sera and feces, respectively, indicating specific mucosal immunity. We also found specific T cell reactivity in mice immunized orally. This approach is paving the way for developing an oral vaccine against CWD.</p>

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PLGA nanoparticles for oral delivery of prion-specific antigen: a novel approach to chronic wasting disease vaccination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月7日

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  • Mohamed M. Elsutohy,
  • Dalia Abdelaziz,
  • Chimoné S. Dalton,
  • Byron Kruger,
  • Shirley Phan,
  • Yo-Ching Cheng,
  • Kevin Low,
  • Hanaa Ahmed-Hassan,
  • Hermann M. Schätzl

摘要

Prion diseases, such as chronic wasting disease (CWD), are incurable, fatal neurodegenerative disorders. We have developed a recombinant dimeric deer prion protein (Ddi) vaccine against CWD that has shown promising immune responses when injected subcutaneously (s.c). While s.c injection is suitable for controlled conditions, oral administration is practical in wildlife. Herein, we have developed an oral vaccine utilizing poly lactic co-glycolic acid (PLGA) nanoparticles, co-encapsulating Ddi and oligodeoxynucleotide adjuvant (CpG) using double emulsion-solvent evaporation technique. Our results showed production of spherical PLGA nanoparticles with size of ~ 200–300 nm, an acceptable surface charge (− 14.2 ± 5.73 mV), and an encapsulation efficiency of approximately 70 and 30%, for Ddi and CpG, respectively. We administered the developed vaccine to FVB mice orally and subcutaneously, followed by ELISA assays of the sera and feces. Mice receiving the vaccine subcutaneously exhibited high antibody reactivities to the used antigen in their sera (100% positivity), with no detectable positive reactivity in their feces. However, those receiving the oral vaccine showed 60 and 80% positivity in sera and feces, respectively, indicating specific mucosal immunity. We also found specific T cell reactivity in mice immunized orally. This approach is paving the way for developing an oral vaccine against CWD.