A recombinant rabies virus chimera expressing the DC-targeting molecular MAB2560 shows enhanced vaccine immunogenicity through activation of dendritic cells

PLoS Negl Trop Dis. 2023 Apr 24;17(4):e0011254. doi: 10.1371/journal.pntd.0011254. eCollection 2023 Apr.

Abstract

Background: Rabies, caused by the rabies virus (RABV), is an ancient and neglected zoonotic disease posing a large public health threat to humans and animals in developing countries. Immunization of animals with a rabies vaccine is the most effective way to control the epidemic and the occurrence of the disease in humans. Therefore, the development of cost-effective and efficient rabies vaccines is urgently needed. The activation of dendritic cells (DCs) is known to play an important role in improving the host immune response induced by rabies vaccines.

Methodology/principal findings: In this study, we constructed a recombinant virus, rCVS11-MAB2560, based on the reverse genetic system of the RABV CVS11 strain. The MAB2560 protein (a DC-targeting molecular) was chimeric expressed on the surface of the viral particles to help target and activate the DCs when this virus was used as inactivated vaccine. Our results demonstrated that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, the inactivated recombinant virus rCVS11-MAB2560 could produce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs more quickly than rCVS11 post immunization.

Conclusions/significance: In summary, the recombinant virus rCVS11-MAB2560 chimeric-expressing the molecular adjuvant MAB2560 can stimulate high levels of humoral and cellular immune responses in vivo and can be used as an effective inactivated rabies vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / metabolism
  • Dendritic Cells
  • Dogs
  • Humans
  • Immunogenicity, Vaccine
  • Mice
  • Rabies Vaccines*
  • Rabies virus*
  • Rabies* / prevention & control

Substances

  • Rabies Vaccines
  • Antibodies, Viral

Grants and funding

This work was founded by the National Natural Science Foundation of China to HW (grant numbers 31872487) and the science and technology development program of Jilin Province to HW (grant numbers 20200402048NC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.