Antibody and B cell responses to Plasmodium sporozoites

Abstract

Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

Keywords: B cells; Plasmodium; antibodies; malaria; pre-erythrocytic stages; sporozoites.

FIGURE 1

The development of memory B cell subsets. Upon encounter with either sporozoite antigen or vaccines, naïve B cells can undergo a variety of different fates. Some develop into short-lived plasmablasts, which give an immediate antibody response to infection. Others may become “early memory” which is germinal center independent, or may enter germinal centers where theirB cell receptors undergo somatic hypermutation and affinity maturation. The germinal center B cells are believed to be the major precursors for long-lived plasma cells, which maintain the circulating antibody pool. Memory cells may be class switched or they may retain the IgM⁺ B cell receptor. The relative contributions of these different memory populations to long term protection against malaria remains an area for further investigation. Figure is based on Taylor et al. (2012). Used with permission from Elsevier.