Frontiers in Immunology (Jan 2023)

A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice

  • Shimeng Bai,
  • Tianhan Yang,
  • Cuisong Zhu,
  • Meiqi Feng,
  • Li Zhang,
  • Ziling Zhang,
  • Xiang Wang,
  • Rui Yu,
  • Xinghao Pan,
  • Chen Zhao,
  • Jianqing Xu,
  • Jianqing Xu,
  • Xiaoyan Zhang,
  • Xiaoyan Zhang

DOI
https://doi.org/10.3389/fimmu.2022.1099991
Journal volume & issue
Vol. 13

Abstract

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BackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.MethodsWe developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.ResultsWe first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.ConclusionOur study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection.

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