Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review

Abstract

Malaria remains a critical global health issue due to high mortality rates, drug resistance, and low treatment efficacy. The genetic variability of Plasmodium proteins complicates the development of long-lasting immunity, as it impedes the human immune system's ability to sustain effective responses. T cells play a crucial role in combating malaria, but the parasite's complex life cycle-spanning liver and blood stages-presents significant challenges in effectively activating and targeting these cells. Immunotherapy, which enhances the immune response and promotes durable T cell activity, offers a promising avenue for more effective and lasting malaria treatments. This review systematically analyzed 63 studies published in the last decade, focusing on the role of T cells in malaria. Among the studies, 87.2% targeted T cells as immunotherapy candidates, with CD4+ and CD8+ T cells each accounting for 47.6% of the studies. γδ T cells were the focus in 7.9% of cases, while 12.7% explored non-T cell contributions to enhancing T cell-mediated responses. The findings underscore the potential of T cells, particularly CD8+ T cells, in liver-stage defense and advocate for the exploration of advanced vaccine platforms and novel therapies, such as mRNA-based vectors and monoclonal antibodies.

Keywords: Plasmodium; T-cell; cell-mediated immunity; immunotherapy; malaria.

Figure 1

T-cell role in malaria infection. This figure depicts the immune response against Plasmodium infection, highlighting the roles of both innate and adaptive immunity, with a focus on T cell activation. Innate immune cells, such as dendritic cells (APCs), are essential for the initial detection of Plasmodium and for initiating adaptive immune responses. T cells, upon activation in the lymph node, contribute to both cellular and humoral immunity. Cellular immunity is primarily mediated by CD8+ cytotoxic T cells and Th1 cells, which target and eliminate infected cells. On the other hand, humoral immunity is facilitated by the activation of B cells through T follicular helper (Tfh) cells, leading to the production of antibodies that provide protection against Plasmodium infection. This integrated immune response is crucial for controlling the parasite and limiting the progression of malaria.

Figure 2

PRISMA-ScR flow diagram for included studies.

Figure 3

T-Cell pre-activation stage.

Figure 4

T-Cell Activation Stage.