Memory T cells maintain protracted protection against malaria

Abstract

Immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. However, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, Plasmodium spp., the causative agents of malaria. For example, memory responses to Plasmodium antigens amongst residents of malaria endemic areas appear to be either inadequately developed or maintained, because persons who survive episodes of childhood malaria remain vulnerable to intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodium sporozoites (γ-spz) induce sterile and long-lasting protection against experimental sporozoite challenge. Multifactorial immune mechanisms maintain this protracted and sterile protection. While the presence of memory CD4 T cell subsets has been associated with lasting protection in humans exposed to multiple bites from Anopheles mosquitoes infected with attenuated Plasmodium falciparum, memory CD8 T cells maintain protection induced with Plasmodium yoelii and Plasmodium berghei γ-spz in murine models. In this review, we discuss our observations that show memory CD8 T cells specific for antigens expressed by P. berghei liver stage parasites as an indispensable component for the maintenance of protracted protective immunity against experimental malaria infection; moreover, the provision of an Ag-depot assures a quick recall of memory T cells as IFN-γ-producing effector CD8 T cells and IL-4- producing CD4 T cells that collaborate with B cells for an effective antibody response.

Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice

“…tended to increase numbers of virus‐specific IFN‐γ + CD4 + and CD8 + T cells. This indicates that vaccination induced and maintained memory T cells, because IFN‐γ, the signature cytokine of Th1 type immune responses, is produced by stimulated T cells and has important immunomodulatory effects . Interestingly, IL17 + CD8 + T cell numbers were increased only by s.l.…”

Montanide, Poly I:C and nanoparticle based vaccines promote differential suppressor and effector cell expansion: a study of induction of CD8 T cells to a minimal Plasmodium berghei epitope

“…The most advanced malaria vaccine development focuses on the pre-erythrocytic stage, at which sporozoite parasites enter the circulation after a mosquito bite and then rapidly enter and infect hepatocytes. CD8 T lymphocytes, particularly those capable of producing interferon gamma (IFN-γ), can mediate effective sterile liver-stage immunity ( Schneider et al, 1999 ; Doolan and Martinez-Alier, 2006 ; Krzych et al, 2014 ). Developing a CD8 T cell inducing liver-stage vaccine would be beneficial to further avoid the clinical symptoms of malaria, such as fever, associated with subsequent blood stages of infection, as well as preventing transmission and the sexual development of parasites ( Arama and Troye-Blomberg, 2014 ).…”

Pre-erythrocytic Stage of Malaria Infection and the Molecular Targets Available for Interventions

“…The major limitation of RTS,S/AS01 is that it is composed of only one surface protein, CSP and may account for its limited efficacy as individuals immunized with irradiated sporozoites has been shown to be associated with sterile protection (Trieu et al, 2011). Furthermore, complexity of the Plasmodium life cycle such that different set of antigens are presented at different stages in the host makes it difficult to design an effective malaria vaccine (de Souza, 2014;Krzych et al, 2014). To this end, there is an urgent need for more detailed understanding of the host and parasite derived proteins which play key roles in the migration and invasion of the parasite at the initial stage (pre-erythrocytic stage) of the infection.…”