CONSEQUENCES OF INTERLEUKIN-21 ON VACCINE INDUCED IMMUNITY BY LIVE RABIES BASED VACCINES. L Kellett, James McGettigan, Department of Microbiology, Thomas Jefferson University, Philadelphia PA.
Greater than two-thirds of the worlds population live in regions where rabies is endemic, resulting in over 15 million people receiving a post-exposure regime and approximately 55,000 deaths per year. The development of a single-dose vaccine would not only reduce the cost of rabies prevention and treatment but save lives globally. B cells secreting virus neutralizing antibodies directed against the rabies virus (RV) glycoprotein (G) are required for protection against infection. Therefore, immunization strategies that augment B cell responses against RV infection may help efforts to develop a single dose vaccine. After exposure to foreign antigen, primed B cells migrate to the B and T cell border of secondary lymphoid tissues where they interact with their cognate T cell. Activated B cells can then migrate into follicular regions of secondary lymphoid organs where they undergo massive proliferation, forming germinal centers (GCs) which generate memory B cells or long-lived plasma cells. Using mice deficient in the IL-21 receptor (IL-21 R-/-), we previously showed the IL-21R signaling is critical for optimal vaccine-induced primary B cell responses and antibody responses against RVG. Here we extended these findings by using reverse genetics to construct, recover and characterize live-replication and replication-deficient RV-based vaccines expressing murine IL-21. Cells infected with recombinant RVs (rRV) expressed high levels of IL-21 in tissue culture supernatants. However, the expression of IL-21 from the rRV did not significantly augment humoral immunity to RV G when compared to the parental virus in mice immunized with various doses or via different routes of inoculation. This suggests that while we previously have shown that IL-21R-defciency hampers RV-specific immunity our current data indicates that RV-based vaccines without the addition of IL-21 induce sufficient levels of IL-21 for protective immunity.