Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immu...Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immunity is the critical first line of host defense against viral infection.It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors,leading to the production of type I interferons(IFNα/β),inflammatory cytokines,and chemokines,or the activation of autophagy or apoptosis to inhibit virus replication.In the case of RABV,the innate immune response is usually triggered when the skin or muscle is bitten or scratched.However,RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system(CNS).Once RABV reaches the CNS,it cannot be wiped out by the immune system or any drugs.Therefore,a better understanding of the interplay between RABV and innate immu-nity is necessary to develop effective strategies to combat its infection.Here,we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.展开更多
Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant...Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines.In this study,we constructed a recombinant virus,rCVS11-LTB,which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit(LTB)protein on the surface of the RABV particles.Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells(DCs).Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virusneutralizing antibodies(VNAs)in both mice and dogs than the parent virus rCVS11,to enhance the cellular immune response and T cell immune memory in mice,and was also able to provide 100%protection in mice from lethal doses of rabies virus,indicating its potential as a safe and effective inactivated rabies vaccine candidate.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:31872487。
文摘Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immunity is the critical first line of host defense against viral infection.It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors,leading to the production of type I interferons(IFNα/β),inflammatory cytokines,and chemokines,or the activation of autophagy or apoptosis to inhibit virus replication.In the case of RABV,the innate immune response is usually triggered when the skin or muscle is bitten or scratched.However,RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system(CNS).Once RABV reaches the CNS,it cannot be wiped out by the immune system or any drugs.Therefore,a better understanding of the interplay between RABV and innate immu-nity is necessary to develop effective strategies to combat its infection.Here,we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.
基金the National Key Research and Development Program of China(No.2022YFD1800100).
文摘Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines.In this study,we constructed a recombinant virus,rCVS11-LTB,which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit(LTB)protein on the surface of the RABV particles.Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells(DCs).Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virusneutralizing antibodies(VNAs)in both mice and dogs than the parent virus rCVS11,to enhance the cellular immune response and T cell immune memory in mice,and was also able to provide 100%protection in mice from lethal doses of rabies virus,indicating its potential as a safe and effective inactivated rabies vaccine candidate.
