Abstract
Cold-chain requirements affect worldwide distribution of many vaccines. In addition, vaccines requiring multiple doses impose logistical and financial burdens, as well as patient compliance barriers. To address such limitations, we have developed new technologies to prepare thermostable, single-shot, prime-boost microparticle vaccines. Antigen/adjuvant formulations containing glass-forming polymers and trehalose first are spray-dried to form glassy microparticles that confer thermostability. Atomic layer deposition (ALD) reactions conducted in fluidized beds are then used to coat the microparticles with defined numbers of molecular layers of alumina that modulate the timed release of the internalized antigen and act as adjuvants. We have used a model HPV16 L1 capsomere antigen to evaluate the properties of these technologies. Thermostabilized powders containing HPV16 L1 capsomeres were prepared by spray-drying, coated by ALD with up to 500 molecular layers of alumina, and injected into mice. Antigen distribution was assessed by live-animal IR dye tracking of injected labeled antigen. Antibody responses were measured weekly by ELISA, and neutralizing antibodies were measured by pseudovirus neutralization assays at selected time points. Thermostability was evaluated by measuring antibody responses after incubating ALD-coated antigen powders for one month at 50 °C. Single doses of the ALD-coated vaccine formulations elicited a prime-boost immune response, and produced neutralizing responses and antibody titers that were equivalent or superior to conventional prime-boost doses of liquid formulations. Antibody titers were unaffected by month-long incubation of the formulations at 50 °C. Single-dose, thermostable antigen preparations may overcome current limitations in HPV vaccine delivery as well as being widely applicable to other antigens.
Highlights
The practical impacts of vaccines are often compromised by common challenges faced in their delivery to patients
Instead of using lyophilization to create glassy powders, mixtures of alum and HPV capsomere protein were spray-dried together with trehalose and hydroxyethyl starch added as glass transition temperature (Tg) modifiers[20,21]
Powders had a water content of
Summary
The practical impacts of vaccines are often compromised by common challenges faced in their delivery to patients. Immunogens and adjuvants are embedded in glassy organic matrices formed from disaccharide-containing mixtures by adjusting lyophilization and formulation parameters in order to control nucleation rates, glass transition temperatures, and other material properties[5]. The process uses controlled, rapid freezing rates combined with addition of relatively high concentrations of formulation excipients such as trehalose or sucrose that rapidly form glasses upon freezing. When these glasses are dried during a lyophilization process, the resulting dry glass powders, which contain embedded antigens, adjuvants, and coadjuvants, become rigid and exhibit slow internal molecular motions. We have optimized these formulations to include starch polymers that raise glass transition temperatures and extend the process to allow spray-drying of these formulations to form glassphase, spherical microparticles in which antigens and adjuvants are encased
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
