Abstract
Several studies have shown that interleukin-18 (IL-18) plays an important role in both innate and adaptive immune responses. In this study, we investigated the pathogenicity and immunogenicity of recombinant rabies virus expressing IL-18 (rHEP-IL18). Experimental results showed that Institute of Cancer Research (ICR) mice that received a single intramuscular immunization with rHEP-IL18 elicited the highest titers of serum neutralizing antibodies and the strongest cell-mediated immune responses to prevent the development of rabies disease, compared with immunization with the parent virus HEP-Flury. Mice inoculated with rHEP-IL18 developed significantly higher IFN-γ responses, increased percentages of CD4+ and CD8+ T-lymphocytes compared to HEP-Flury. Flow cytometry results show that rHEP-IL18 recruited more activated T- and B-cells in lymph nodes or peripheral blood, which is beneficial for virus clearance in the early stages of infection. A higher percentage of mice immunized with rHEP-IL18 survived wild-type rabies virus (RABV) challenge, compared to HEP-Flury mice. Our results show that rHEP-IL18 is promising as a novel vaccine for RABV prevention and control.
Highlights
Rabies is a fatal zoonotic infectious disease caused by rabies virus (RABV) and afflicts most mammalian hosts [1, 2]
Experimental results showed that Institute of Cancer Research (ICR) mice that received a single intramuscular immunization with rHEP-IL18 elicited the highest titers of serum neutralizing antibodies and the strongest cell-mediated immune responses to prevent the development of rabies disease, compared with immunization with the parent virus HEP-Flury
In order to improve the efficacy of RABV vaccines, several cytokines have been trialed as adjuvants to improve immune responses, including MIP-1α, MDC and GM-CSF [29, 30]
Summary
Rabies is a fatal zoonotic infectious disease caused by rabies virus (RABV) and afflicts most mammalian hosts [1, 2]. Livewww.impactjournals.com/oncotarget attenuated RABV vaccines and recombinant live vaccines have already been licensed, such as a recombinant vaccinia virus expressing the RABV G protein (VRG) and a live avirulent RABV, SAG-2, for wild animals [14,15,16,17]. These vaccines provide effective immunization with a single dose and has practical, economical, and logistical advantages over conventional multi-dose vaccines with respect to the goal of eradicating rabies worldwide [16, 18,19,20,21]. Live-attenuated RABV vaccines can induce immune responses to clear virulent RABV from the CNS and there is the possibility that such vaccines could serve as the foundation for the treatment of early stage human rabies infections [22, 23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
