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

ABSTRACT

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.