Many vaccines use a weakened or engineered form of a pathogenic virus to generate an immunogenic response, which helps prepare the immune system against a real infection from that virus. Being proteinaceous therapeutics, however, these vaccines denature when exposed to elevated temperatures or organic solvents. In 2016 we published a communication showing how the surfaces of virus like particles could nucleate the growth of a crystalline porous coordination polymer called zeolitic imidazolate framework-8 (ZIF-8). In addition, we showed that the ZIF-8 shell can stabilize tobacco mosaic virus (TMV) against harsh conditions and after the ZIF-8 shell is removed by EDTA exfoliation the virus retains its rod-like shape. Many questions, however, persisted including i) what effect did the nucleation and growth of ZIF-8 have on the surface of the virus, ii) if the viral nanoparticle RNA was likewise protected against degradation, and iii) how this technology could be translated to in vivo use. I will present recently published work that gave us answers to these questions: To address i) TMV or encapsulated TMV (TMV@ZIF) was stressed under various conditions and measured by ELISA. The results indicated that the ZIF-8 shell improves the surface stability of TMV compared to the unencapsulated virus when boiled in water for 20 min by 164.97% and when left in methanol, 6 M guanidinium chloride, or ethyl acetate overnight by 55.42 %, 199.24 %, and 18.33%, respectively. To address ii) we infected Nicotiana benthamiana plants with TMV@ZIF or exfoliated TMV@ZIF and after 10 days the leaves were harvested for measurements by ELISA. Plants infected with TMV@ZIF showed an ELISA response at 66.6% and exfoliated TMV@ZIF at 72.2%, indicating that the RNA is protected against degradation—KP buffer (0 %) and TMV (100 %) were used as controls. To address iii), Cy5 labeled TMV (Cy5-TMV) was encapsulated (Cy5-TMV@ZIF) and injected subcutaneously into mice to evaluate the dispersal over time. Cy5-TMV@ZIF remained fluorescent 7 days longer than Cy5-TMV owing to the slow dissolution of ZIF-8, which exposes antigen presenting cells to the virus longer, leads to a stronger immunogenic response, and the histological analysis showed no signs of toxicity. Upon completion of this study, we now strongly believe that biomimetic mineralization can eliminate the need to refrigerate proteinaceous therapeutics.

Enhanced immunogenic response of biomimetic mineralized vaccines

2019 Fall National Meeting

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