ABSTRACT Aluminum adjuvants have been used in licensed human vaccines for almost a century. However, they can neither induce an efficient cellular immune response, nor be frozen or lyophilized due to aggregation and diminished adjuvant efficacy. This study developed a series of lyophilizable nano‐aluminum adjuvants by coating nanoscale aluminum adjuvant (Adju‐Phos) with glycol chitosan (GCS, 20 kDa) using microfluidics technology. When the GCS/alum weight ratio was higher than 4:1, the nano‐aluminum adjuvants withstood autoclaving and freeze‐drying treatments in the presence of trehalose without significant physicochemical changes. Moreover, the lyophilized nano‐aluminum adjuvants remained stable for 15 months at room temperature. When combined with HPV16 L1 virus‐like particles (VLPs), the nano‐aluminum adjuvant with 7:1 GCS/alum weight ratio (G7‐A1) elicited stronger adaptive immunity, as evidenced by higher neutralizing antibodies, balanced IgG1/IgG2c ratio, elevated IFN‐γ/TNF‐α/IL‐4/IL‐10 secretion, and increased Th1/CTL/memory T cell frequencies. Furthermore, combining G7‐A1 with MF59‐like emulsion or C‐di‐AMP enhanced antigen‐specific humoral and cellular immunity, memory T cell responses, and dendritic cell activation. These findings demonstrate the great potential of nano‐aluminum adjuvants in improving vaccine efficacy, and suggest that they may serve as alternatives suitable for vaccines requiring balanced Th1/Th2 immunity or strong cellular immunity.
Zhou et al. (Sat,) studied this question.