Bacillus subtilis vector based oral rabies vaccines induced potent immune response and protective efficacy in mice

Ying Zhang; Ruo Mo; Sheng Sun; Zhanding Cui; Bo Liang; Entao Li; Tiecheng Wang; Ye Feng; Songtao Yang; Feihu Yan; Yongkun Zhao; Xianzhu Xia

doi:10.3389/fmicb.2023.1126533

Bacillus subtilis vector based oral rabies vaccines induced potent immune response and protective efficacy in mice

Front Microbiol. 2023 Feb 9:14:1126533. doi: 10.3389/fmicb.2023.1126533. eCollection 2023.

Authors

Ying Zhang^{1

2}, Ruo Mo^{2

3}, Sheng Sun², Zhanding Cui⁴, Bo Liang², Entao Li⁵, Tiecheng Wang², Ye Feng², Songtao Yang², Feihu Yan², Yongkun Zhao², Xianzhu Xia^{1

2}

Affiliations

¹ Northeast Forestry University College of Wildlife and Protected Area, Harbin, China.
² Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China.
³ College of Veterinary Medicine, Jilin Agricultural University, Changchun, Jilin, China.
⁴ State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
⁵ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Abstract

Introduction: Rabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine.

Methods: We constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice.

Results: The results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.

Keywords: Bacillus subtilis; G protein; oral immunization; oral rabies vaccine; rabies.