Nano alum: A new solution to the new challenge

Alum adjuvant has always been the first choice when designing a vaccine. Conventional aluminum adjuvant includes aluminum hydroxide, aluminum phosphate, and amorphous aluminum hydroxyphosphate (AAHS), which could effectively induce the humoral, and to a lesser extent, cellular immune responses. Their safety is widely accepted for a variety of vaccines. However, conventional alum adjuvant is not an ideal choice for a vaccine antigen with poor immunogenicity, especially the subunit vaccine in which cellular response is highly demanded. The outbreak of COVID-19 requires a delicately designed vaccine without the antibody-dependent enhancement (ADE) effect to ensure the safety. A sufficiently powerful adjuvant that can induce both Th(1) and Th(2) immune responses is necessary to reduce the risk of ADE. These circumstances all bring new challenges to the conventional alum adjuvant. However, turning conventional microscale alum adjuvant into nanoscale is a new solution to these problems. Nanoscale alum owns a higher surface volume ratio, can absorb much more antigens, and promote the ability to stimulate the antigen-presenting cells (APCs) via different mechanisms. In this review, the exceptional performance of nano alum adjuvant and their preparation methods will be discussed. The potential safety concern of nano alum is also addressed. Based on the different mechanisms, the potential application of nano alum will also be introduced.