Giving it its Best Shot: Quality Control of Antiviral Vaccines with the Litesizer

The particle size of vaccines has a considerable influence on their half-life in vivo, as well as on their uptake by antigen-presenting cells. The surface charge of particles is also suspected of influencing the same parameters. Here we use DLS and ELS to characterize respectively the particle size and zeta potential of two inactivated antiviral vaccines.

Introduction

Vaccines often constitute the only line of defense against viral infections, as the range of antiviral drugs currently available and treatment success are limited. The situation is different for bacterial infections, where antibiotics are an efficient therapeutic intervention.

Antiviral vaccines can consist of live-attenuated viral particles, which produce a low-noise infection in the recipient. While this strategy is able to mimic an infection by the pathogen very closely, and generally triggers a very robust immune response, it has the potential for serious side effects in immunocompromised individuals.

Thus, a majority of antiviral vaccines now consist in formulations which do not have the potential for replication in the host. These range from chemically inactivated whole or split viruses, to recombinant proteins or virus-like particles produced by genetic engineering. While these vaccines have a better safety profile, they also tend to trigger weaker immune responses than their live-attenuated counterparts. Hence, many of them are administered together with so-called vaccine adjuvants, which increase the efficacy and longevity of the immune response.

The oldest and still most popular such adjuvant is aluminum salt (e.g., aluminum hydroxide or aluminum hydroxyphosphate). Its immuno-stimulatory properties are believed to be linked both to its capacity to adsorb and retain antigens for long periods at the site of injection, and to its ability to trigger the local release of pro-inflammatory mediators (1).

The particle size of a vaccine has a significant impact on its immunogenicity. With few exceptions, viruses are nanoparticles ranging in size from 15 to 300 nm. Upon injection, particles in this size range are efficiently taken up by dendritic cells, a class of sentinel cells uniquely endowed with the ability to induce both antibody- and killer cell-mediated immunity (2). In contrast, particles in the micrometer range, such as aluminum salt particles (1), are preferentially taken up by monocytes and macrophages, which predominantly induce an antibody-mediated immune response. 

References

1. Shardlow E., Mold M. & Exley C. (2017). From stock bottle to vaccine: elucidating the particle size distributions of aluminum adjuvants using dynamic light scattering. Frontiers in Chemistry 4:48.

2. Etchart N., et al. (2001). Dendritic cells recruitment and in vivo priming of CD8+ CTL induced by a single topical or transepithelial immunization via the buccal mucosa with measles virus nucleoprotein. Journal of Immunology 167:384-391.

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