Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery

Abstract

Subunit vaccines are composed of pathogen fragments that, on their own, are generally poorly immunogenic. Therefore, the incorporation of an immunostimulating agent, e.g. adjuvant, into vaccine formulation is required. However, there are only a limited number of licenced adjuvants and their immunostimulating ability is often limited, while their toxicity can be substantial. To overcome these problems, a variety of vaccine delivery systems have been proposed. Most of them are designed to improve the stability of antigen in vivo and its delivery into immune cells. Cell-penetrating peptides (CPPs) are especially attractive component of antigen delivery systems as they have been widely used to enhance drug transport into the cells. Fusing or co-delivery of antigen with CPPs can enhance antigen uptake, processing and presentation by antigen presenting cells (APCs), which are the fundamental steps in initiating an immune response. This review describes the different mechanisms of CPP intercellular uptake and various CPP-based vaccine delivery strategies.

Keywords: Cell-penetrating peptide; adjuvant; antigen presenting cells; antigen uptake; humoral and cellular immunity; vaccine delivery..

Fig. (1)

Non-endocytic CPP uptake mechanisms: A) barrel-stave model; B) toroidal model; C) inverted micelle; D) carpet model.

Fig. (2)

Endocytic CPP-cargo uptake pathways: A) macropinocytosis; B) clathrin-mediated endocytosis; C) caveloae-mediated endocytosis; D) phagocytosis.

Fig. (3)

Diagrammatic representation of the major immune response pathways.