Single-administration, thermostable human papillomavirus vaccines prepared with atomic layer deposition technology

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.

Elastic Bioresorbable Polymeric Capsules for Osmosis-Driven Delayed Burst Delivery of Vaccines

“…Appropriate considerations would have to be made regarding the storage of other payloads during the delay period, and the suitability of the nature of the burst of the devices for that application. Since that study five years ago, research into biomaterials-based solutions for single-administration vaccination has been ongoing, predominantly in the form of microparticles [ 13 , 14 ], and microneedle arrays [ 15 , 16 ]. In that time, the use of osmosis as a trigger for delayed burst release has remained relatively unexplored, with only a conceptual demonstration of such release from PLGA spheres [ 44 ].…”

“…Development of non-injectable delivery routes such as oral and intranasal delivery have been attempted, but only a limited few have shown clinical and regulatory success to date [ 10 , 11 , 12 ]. Most of the proposed SAV solutions employ resorbable biomaterials to delay the release of (a part of) the antigen, e.g., in the form of injectable microparticles [ 13 , 14 ] or transdermal microneedle arrays [ 15 , 16 ]. We previously introduced an alternative approach, using an implantable monolithic polymer capsule that contains the vaccine dose and an osmotically active agent [ 17 ].…”

COVID-19 pandemic: SARS-CoV-2 specific vaccines and challenges, protection via BCG trained immunity, and clinical trials

“…Moreover, the BCG vaccine price is relatively low, and even in some developing countries, governments provide free vaccination services, which dramatically increases the accessibility and affordability of the BCG vaccine. If the clinical trial results support the hypothesis that BCG can effectively prevent COVID-19, the BCG vaccine will solve many challenges faced by currently available COVID-19 vaccines, such as multiple doses imposing financial burdens and patient compliance barriers [ 106 ].…”

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…For this, it is not surprising that the spray-drying of diverse types of vaccines has gathered the deep interest of various research groups. [71,[117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] In Figure 3, we present the chronological trends of the studies in the spray-drying of protein pharmaceuticals. We can observe an extensive research of peptide hormones during 2002-2011, and their numbers dwindling slightly in recent years.…”