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

• Published in: PLoS neglected tropical diseases Vol. 17; no. 4; p. e0011254
• Main Authors: Gong, Zhiyuan, Huang, Pei, Jin, Hongli, Bai, Yujie, Li, Hailun, Qian, Meichen, Sun, Jingxuan, Jiao, Cuicui, Zhang, Mengyao, Li, Yuanyuan, Zhang, Haili, Wang, Hualei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2023; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antibodies; Antibodies, Viral - metabolism; Biology and Life Sciences; Care and treatment; Cell activation; Cell proliferation; Cells; Deactivation; Defence mechanisms; Dendritic Cells; Developing countries; Diagnosis; Disease control; Disease transmission; Dogs; Epidemics; Health aspects; Health risks; Humans; Immune response; Immune response (cell-mediated); Immune response (humoral); Immune system; Immunity; Immunization; Immunogenicity; Immunogenicity, Vaccine; Immunological memory; Kinases; LDCs; Lymphocytes; Lymphocytes B; Lymphocytes T; Medicine and Health Sciences; Memory cells; Mice; Plasmids; Proliferation; Public health; Rabies; Rabies - prevention & control; Rabies Vaccines; Rabies virus; Recombinants; Research and Analysis Methods; Tropical diseases; Vaccines; Viruses; Zoonoses; China; United States > US
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011254

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. 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. 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.