Recombinant rabies virus expressing IL-21 enhances immunogenicity through activation of T follicular helper cells and germinal centre B cells

Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signalling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that in mice immunized with LBNSE-IL21, there was a substantial increase in the number of T follicular helper cells and germinal centre B cells but no enhancement of dendritic cell activation. Furthermore, significantly higher rabies virus-neutralizing antibody (VNA) titres were produced in mice immunized with LBNSE-IL21 than in mice immunized with the parent virus LBNSE in the first six weeks, resulting in higher protection. Together, these results suggest that LBNSE-IL21 can induce a rapid and robust VNA titre, and it has the potential to be developed as a promising rabies vaccine.