Vaccine · 2025
A single ultra-low dose self-amplifying RNA rabies vaccine confers rapid and complete protection in mice.
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Zhao Danhua, Chen Geng, Wang Shanshan, Suo Yue, Ye Qiang, Xing Rui, Yang Yongjun, Li Zhi, XuelianWang, Zhou Rui, Ma Li, Cao Shouchun, Wu Xiaohong, Hu Yangbo, Xiong Changyun, Wang Youru
Аннотация
PURPOSE: Rabies is a fatal zoonotic disease caused by the Rabies virus (RABV), resulting in approximately 59,000 deaths globally each year. Of these fatalities, 95 % occur in impoverished regions across Asia and Africa where medical resources are scarce, with children accounting for as much as 40 % of the total cases. To address the logistical challenges of current inactivated rabies vaccines-such as the complexities of multi-dose regimens and manufacturing constraints-this study aimed to develop a rabies vaccine based on a self-amplifying mRNA (saRNA) platform, which offers potential advantages in rapid protection, scalable production, and dose-sparing capacity.
METHODS: An optimized saRNA encoding the rabies glycoprotein was constructed. In SPF BALB/c mice, immunogenicity and protective efficacy against 100 LD₅₀ intracranial CTN-1 challenge were evaluated after single-dose (0.0008-1 μg) or two-dose regimens, with particular attention to early protection at days 7 and 14 post-immunization.
RESULTS: A single administration of 0.1 μg saRNA vaccine delivered 100 % survival upon challenge at day 14 (62.5 % at day 7), accompanied by high-titer neutralizing antibodies and robust T-cell activation. This effective dose is 15-fold lower than previously reported values. A two-dose schedule between day 0 and day 7 further reduced the dose required for 100 % protection by 80 %, from 0.1 μg to 0.02 μg.
CONCLUSIONS: The optimized saRNA rabies vaccine achieves complete protection within 14 days after a single microgram-level dose, or after two ultra-low doses, outperforming traditional inactivated vaccines and offering an efficient regimen for simplified post-exposure prophylaxis.
METHODS: An optimized saRNA encoding the rabies glycoprotein was constructed. In SPF BALB/c mice, immunogenicity and protective efficacy against 100 LD₅₀ intracranial CTN-1 challenge were evaluated after single-dose (0.0008-1 μg) or two-dose regimens, with particular attention to early protection at days 7 and 14 post-immunization.
RESULTS: A single administration of 0.1 μg saRNA vaccine delivered 100 % survival upon challenge at day 14 (62.5 % at day 7), accompanied by high-titer neutralizing antibodies and robust T-cell activation. This effective dose is 15-fold lower than previously reported values. A two-dose schedule between day 0 and day 7 further reduced the dose required for 100 % protection by 80 %, from 0.1 μg to 0.02 μg.
CONCLUSIONS: The optimized saRNA rabies vaccine achieves complete protection within 14 days after a single microgram-level dose, or after two ultra-low doses, outperforming traditional inactivated vaccines and offering an efficient regimen for simplified post-exposure prophylaxis.