Optimized Formulation of a Thermostable Spray-Dried Virus-Like Particle Vaccine against Human Papillomavirus

• Published in: Molecular pharmaceutics Vol. 13; no. 5; pp. 1646 - 1655
• Main Authors: Saboo, Sugandha, Tumban, Ebenezer, Peabody, Julianne, Wafula, Denis, Peabody, David S, Chackerian, Bryce, Muttil, Pavan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.05.2016
• Subjects: Animals; Antibodies, Neutralizing - immunology; Chemistry, Pharmaceutical - methods; Humans; Immunization - methods; Immunoglobulin G - immunology; Mice; Mice, Inbred BALB C; Papillomaviridae - immunology; Papillomavirus Infections - immunology; Powders - administration & dosage; Powders - chemistry; Temperature; Vaccination - methods; Vaccines, Virus-Like Particle - chemistry; Vaccines, Virus-Like Particle - immunology; thermostable vaccine; virus-like particles; design of experiment; spray drying; cold-chain; dry powder
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.6b00072

Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP)-based vaccine for HPV infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multicomponent excipient system and by optimizing the spray-drying parameters using a half-factorial design approach. Dry-powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry-powder VLPs that were stored at 37 °C for more than a year elicited high anti-L2 IgG antibody titers. Spray-dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ∼84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage.