title: Towards preserving the immunogenicity of protein antigens carried by nanoparticles while avoiding the cold chain.
abstract: Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37 degrees C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, United States.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Sloat
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandoval
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000818:Animals; D022122:Anthrax Vaccines / Q000737:chemistry / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D003080:Cold Temperature; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D005240:Feasibility Studies; D005260:Female; D005612:Freeze Drying; D005989:Glycerides / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D011205:Povidone / Q000737:chemistry; D011487:Protein Conformation; D055550:Protein Stability; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004337:Drug Carriers; D005079:Excipients; D005989:Glycerides; D054709:Lecithins; C030325:anthrax toxin; C048159:glyceryl monostearate; D012710:Serum Albumin, Bovine; D008353:Mannitol; D011205:Povidone