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

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. Author summary Due to the lack of effective treatments and drugs, rabies is still an important zoonotic disease, posing a great risk to animals and human public health in developing countries. Vaccines, especially inactivated vaccines, are currently the most effective way to prevent and control the rabies epidemic. Here, we constructed a recombinant virus rCVS11-MAB2560 chimeric-expressed MAB2560 protein (a DC-targeting molecular) on the surface of the RABV particles to promote its immunogenicity in vivo by activating the dendritic cells (DCs) and enhancing antigen uptake. Our results showed 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, compared with rCVS11, the inactivated recombinant virus rCVS11-MAB2560 could induce higher level of virus-neutralizing antibodies (VNAs) in mice and dogs more quickly post immunization. rCVS11-MAB2560 thus has potential to be used as a promising candidate for an effective inactivated rabies vaccine.