Proanthocyanidins-based adjuvant for enhanced immune responses of SARS-CoV-2 subunit vaccine

Aluminum-containing adjuvants have been widely used in human vaccines, such as anti-COVID-19 vaccine, to enhance antigen-specific immune responses. However, a major limitation of aluminum adjuvants in clinical application is that they typically enhance humoral immune responses but have weaker effects on cellular immune responses. Therefore, there has been a continuous and active pursuit of novel adjuvants that can address the shortcomings of traditional adjuvants and improve vaccine efficacy. In this paper, we proposed a novel vaccine-adjuvant system utilizing the convenient physical mixing of natural proanthocyanidins (PCs) and its derivative with a recombinant RBD subunit vaccine, which induced comparable humoral immune responses compared to aluminum adjuvant. In the context of cellular immunity, PCs modified with 4-bromomethyl phenylboronic acid not only enhanced the maturation and migration of dendritic cells but also improved the antigen uptake and presentation capacity of monocytes, leading to robust activation of immune cells, particularly involving CD4(+) and CD8(+) T cells, thereby demonstrating a clear Th1/CTL response bias. In general, PCs andtheir derivatives could be potential innovative natural adjuvants which effectively balance the Th1/Th2 immune response to recompense for the deficiency of aluminum adjuvant, and our study also offers an approach to discovering safe and efficient natural adjuvants.