H7 Hemagglutinin nanoparticles retain immunogenicity after >3 months of 25°C storage.

Timothy Z Chang,Julie A Champion,Lei Deng,Bao-Zhong Wang,Stephen Mark Tompkins

doi:10.1371/journal.pone.0202300

Timothy Z Chang, Julie A Champion + Show 3 more

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https://doi.org/10.1371/journal.pone.0202300

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Abstract

Vaccine distribution infrastructure remains inadequate in many parts of the world, and it is estimated that up to 40–50% of all vaccine doses are wasted in certain countries. Vaccines that can maintain viability outside of the cold chain would decrease vaccine wastage and increase immunization rates in regions of the world with underdeveloped vaccine distribution infrastructure. We examined the potential of crosslinked protein nanoparticles, made from trimerized influenza hemagglutinin (3HA), to maintain immunogenicity after cold-chain-independent storage. We found that the nanoparticles could be stored for 112 days at room temperature without any loss in hemagglutinating activity or immunogenicity, and that nanoparticles could be stored at 37°C for 2 weeks without any loss in hemagglutinating activity. As vaccine development moves towards the use of recombinant subunit antigens, our results demonstrate the potential of crosslinked antigen nanoparticles as an immunogenic vehicle for bringing effective vaccines to underdeveloped regions outside of the cold chain.

Highlights

Despite advances in vaccine development, vaccine distribution infrastructure remains inadequate in many parts of the world, and it is estimated that up to 40–50% of all vaccine doses are wasted in certain countries[1]
Nanoparticles stored in phosphate-buffered saline (PBS) at room temperature did not lose agglutinating activity or appreciably change in size after 112 days, while nanoparticles stored at 37 ̊C retained full hemagglutinating activity for 2 weeks, and lost activity at 1 month (Fig 1A and 1B)
Soluble 3HA in PBS showed similar stability to nanoparticles when stored at room temperature; no hemagglutinating activity losses were observed after 56 days

Summary

Introduction

Despite advances in vaccine development, vaccine distribution infrastructure remains inadequate in many parts of the world, and it is estimated that up to 40–50% of all vaccine doses are wasted in certain countries[1]. Strict control of temperature is important for whole pathogen vaccines, as these are prone to stability losses[2]. Pathogens with lipid membranes, such as bacteria and certain viruses including influenza, are especially prone to osmotic stress, and changing salt concentrations due to temperature-driven solvent evaporation can lead to pathogen shrinkage and destruction[2, 3]. The development of vaccines that can maintain viability outside of the cold chain would decrease vaccine wastage and increase immunization rates in regions of the world with underdeveloped vaccine distribution infrastructure.

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Conclusion