A QS21+ CpG-Adjuvanted Inactivated Vaccine Elicits Superior Humoral and Moderate Cellular Immunity.

Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. Inactivated vaccines without any adjuvants are the sole vaccines licensed for the prophylaxis of rabies. We developed a novel QS21+CpG-adjuvanted inactivated vaccine and systematically compared its performance against inactivated vaccine and Alum-adjuvanted inactivated vaccine. The result shows the QS21+CpG-adjuvanted inactivated vaccine elicited superior humoral immunity, as evidenced by significantly higher RABV-specific IgG titers and virus-neutralizing antibody responses compared to all other groups. The QS21+CpG-adjuvanted inactivated vaccine maintained its expected cellular immunity advantage, with significantly increased frequencies of IFN-γ- and IL-2-secreting splenocytes, as well as elevated IFN-γ and IL-2 levels in splenocyte culture supernatants. Both QS21+CpG and Alum-adjuvanted inactivated vaccine groups provided 100% protection against lethal challenge. These findings provide novel adjuvant strategies for licensed inactivated rabies vaccines and offer critical insights for pathogens requiring robust humoral and Th1-biased cellular immunity.