Investigating the Role for IL-21 in Rabies Virus Vaccine-induced Immunity

Over two-thirds of the world's population lives in regions where rabies is endemic,resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (pep) and over 55,000 deaths per year globally. a major goal in rabies virus (rabv) research is to develop a single-dose pep that would simplify vaccination protocols,reduce costs associated with rabv prevention,and save lives. protection against rabv infections requires virus neutralizing antibodies; however,factors influencing the development of protective rabv-specific b cell responses remain to be elucidated. here we used a mouse model of il-21 receptor-deficiency (il-21r-/-) to characterize the role for il-21 in rabv vaccine-induced immunity. il-21r-/- mice immunized with a low dose of a live recombinant rabv-based vaccine (rrabv) produced only low levels of primary or secondary anti-rabv antibody response while wild-type mice developed potent anti-rabv antibodies. furthermore,il-21r-/- mice immunized with low-dose rrabv were only minimally protected against pathogenic rabv challenge,while all wild-type mice survived challenge,indicating that il-21r signaling is required for antibody production in response to low-dose rabv-based vaccination. il-21r-/- mice immunized with a higher dose of vaccine produced suboptimal anti-rabv primary antibody responses,but showed potent secondary antibodies and protection similar to wild-type mice upon challenge with pathogenic rabv,indicating that il-21 is dispensable for secondary antibody responses to live rabv-based vaccines when a primary response develops. furthermore,we show that il-21 is dispensable for the generation of tfh cells and memory b cells in the draining lymph nodes of immunized mice but is required for the detection of optimal gc b cells or plasma cells in the lymph node or bone marrow,respectively,in a vaccine dose-dependent manner. collectively,our preliminary data show that il-21 is critical for the development of optimal vaccine-induced primary but not secondary antibody responses against rabv infections. © 2013 dorfmeier et al.