Application of polyhedrin protein microparticles for in vivo vaccine and biologics delivery: a proof-of-concept study
Despite significant advancements in preventative and therapeutic strategies against viral infections, further improvements in global management of diseases require ongoing innovations to address long standing as well as newly emerging problems. For example, inherent vaccine instability results in strict cold-chain maintenance guidelines to preserve vaccine efficacy, which in turn increases costs. Consequently, underserved healthcare systems are often unable to afford vaccination programmes. In the case of biologic based antivirals, chemical modifications such as the conjugation of polyethylene glycol (PEG) and its derivates, are commonly used to increase drug potency. However, recent studies have reported an increase in anti-PEG immunity within the general population due to the widespread use of PEG not only in medicine but also cosmetics and foods, resulting in in the termination of several clinical trials due to adverse effects linked to high anti-PEG antibody titres. In this study, we assess the utilisation of polyhedrin protein based nanoparticles, for *in vivo* delivery of vaccines and biologics. The polyhedrin crystal phenomenon is naturally found within the life-cycle of insect viruses, whereby the encapsulation of mature viral particles by polyhedrin crystals enables the insect viruses to survive degradation in harsh environments prior to infection with a new host. Using protein tags derived from a polyhedrin expressing insect virus, we develop novel polyhedrin based Norovirus and Zika virus nanoparticle vaccines, as well as IFN-λ nanoparticles. We highlight the potential to utilise this technology in medicine. Firstly, we demonstrate the possibility to induce high titres of neutralising Norovirus antibodies. Secondly, we confirm thermostable properties of polyhedrin based nanoparticles in retaining immunogenic properties in Zika vaccine immunisation in mice. Finally, we characterise the retainment of antiviral properties in tagged IFN-λ in vitro, prior to their encapsulation. We also outline major limitations and issues faced due to the relative immaturity of this novel technology, and discuss important considerations for future improvements and adaptations.
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