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

NPJ Vaccines
Robert L GarceaTheodore W Randolph

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 ...Continue Reading

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Citations

Sep 15, 2020·Expert Opinion on Drug Delivery·Emrullah KorkmazLouis D Falo
Jul 1, 2020·Advanced Drug Delivery Reviews·Darrell J IrvineMurillo Silva
Jan 24, 2021·Advanced Drug Delivery Reviews·Kendall B Preston, Theodore W Randolph

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Methods Mentioned

BETA
flow imaging
flow imaging microscopy
scanning
transmission electron microscopy
ELISA
size exclusion chromatography
differential scanning calorimetry
fluorescence imaging
transfection

Software Mentioned

Python
VisualSpreadsheet

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