Mechanisms of adaptive immunity to Plasmodium liver-stage infection: The known and unknown

Abstract

The potential of vaccine-induced adaptive immune responses to limit Plasmodium liver-stage infection has been appreciated for decades, but to date, there are no licensed vaccines that induce sterilizing immunity. The most potent vaccine-induced immune mediators of protection have been determined to be antibodies and CD8 T cells targeting sporozoite and liver-stage antigens. Most of this information was generated through evaluation of whole sporozoite vaccination (WSV) approaches, but application of WSV to human vaccination in the field is complicated. To date, subunit vaccination approaches in humans have not led to similar success in protection as WSV. Here, we highlight the protective attributes of anti-Plasmodium antibodies, CD8 T cells, and CD4 T cells learned primarily through mouse models of malaria and WSV as well as targeted subunit vaccination approaches. Finally, we suggest future areas of research that may reveal pertinent information in order to improve adaptive immune responses and protection from Plasmodium through subunit vaccine approaches.