Rational design of an influenza subunit vaccine powder with sugar glass technology: Preventing conformational changes of haemagglutinin during freezing and freeze-drying

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

“…In contrast, our study showed that trehalose protected HA activity of influenza VLPs better than dextran and glucose and much better than inulin during the air drying process used here. Amorij et al reported that visible aggregates were detected in a hemagglutinin vaccine lyophilized in PBS without carbohydrate after reconstitution (40). Thus, we hypothesize that influenza VLPs may similarly have been protected by trehalose during drying by preventing aggregation of VLP particles.…”

“…In contrast, other studies have assessed conformational changes of soluble hemagglutinin subunit vaccines by fluorescence and circular dichroism spectroscopy and found changes in secondary helical conformation and tertiary structure of hemagglutinin upon freezing in PBS (40). However, unlike soluble hemagglutinin protein, VLPs resemble the wildtype virus in structure and morphology.…”

“…In particular, the addition of trehalose preserved 100% HA activity of influenza VLPs in the absence of CMC and approximately 50-60% in the presence of CMC after drying. Carbohydrates have previously been shown to protect the structural integrity of soluble hemagglutinin during lyophilization, perhaps due to the formation of an amorphous glassy state after freeze drying, as shown by differential scanning calorimetry analysis (40). Other studies have similarly shown that the activity of various influenza vaccine was similarly retained after freeze drying in the presence of carbohydrates, including trehalose, dextran, and inulin (38,41,42).…”

Simplifying Influenza Vaccination During Pandemics: Sublingual Priming and Intramuscular Boosting of Immune Responses with Heterologous Whole Inactivated Influenza Vaccine

“…The NIBRG-14 vaccine was freeze-dried as described previously (19). In brief, the vaccine was mixed with an aqueous inulin solution with a HA: inulin weight ratio of 1:500 and a final inulin concentration of 5% w/v.…”

“…Influenza vaccines can be stabilized by incorporating them into a glassy matrix of a sugar, e.g., inulin, dextran, or trehalose, for example, by means of freeze-drying techniques (19)(20)(21)(22). Dried vaccines can be reconstituted prior to intramuscular (i.m.)…”