Host-Pathogen Interaction Interface: Promising Candidate Targets for Vaccine-Induced Protective and Memory Immune Responses

Abstract

Vaccine formulations are a successful strategy against pathogen transmission because vaccine candidates induce effective and long-lasting memory immune responses (B and CD4+ T cells) at systemic and mucosal sites. Extracellular vesicles of lipoproteins, bioactive compounds from plants and invertebrates (sponges) encapsulated in liposomes, and glycoproteins can target these sites. The vaccine candidates developed can mimic microbial pathogens in a way that successfully links the innate and adaptive immune responses. In addition, vaccines plus adjuvants promote and maintain an inflammatory response. In this review, we aimed to identify the host-pathogen interface as a rich source of candidate targets for vaccine-induced protective and long-lasting memory immune responses.

Keywords: Gram-negative pathogenic bacteria; Gram-positive; adjuvants; cellular immune response; innate; prime boost; route of immunization; vaccines.

Figure 1

The membrane surface of Gram-positive and Gram-negative bacteria is composed of a number of molecular components that shape the interaction with the host. Lipopolysaccharides (LPS), peptidoglycans, mycolic acids, and toxins are known as pathogen-associated molecular patterns or PAMPs. Transmembrane pumping systems, such as porins and the secretory two-system component, allow bacteria to secrete antimicrobial peptides, all of which are potential vaccine candidates whose design, based on nanotechnology and various multi-omics technologies, opens up the range of possibilities from genome mining to the optimization of even artificial intelligence to predict candidate vaccine formulations for the induction of long-lasting memory and protective immune responses.

Figure 2

Schematic representation of the host–pathogen interaction interface. The interaction at the interface is between the pathogen and the host and the interaction is mediated by the pathogen-associated molecular patterns (PAMPS) and the patterns of receptor recognition (PRRs) on the surface of antigen-presenting cells (APCs). The vast majority of pathogens are airborne. When an antigen enters the body by the intramuscular/subcutaneous route, it reaches the inductive sites in the lymph nodes and elicits a systemic immune response, but does not activate the mucosal immune system. However, if the antigen enters via the nasal/oral route, it reaches the inductive sites in the gut and there are two possibilities: (1) the induction of a systemic immune response and (2) a mucosal cellular immune response. There is also induction of chemokines and cytokines and the expression of homing receptors. The vaccine candidates mimic the pathogens and follow a similar pathway for the induction of systemic or mucosal protective and immune responses, depending on the formulations. Vaccines targeting one of the mucosal compartments (BALT, NALT, MALT, and GALT) require a particulate formulation, such as exo-vesicles, exosomes, liposomes, plus the adjuvant. Current vaccines against microbial or viral pathogens are listed on the left.

Figure 3

Vaccine induced protective and memory immune responses. Vaccines mimic the pathogen-induced immune response when administered by the systemic or mucosal route. In subcutaneous/intramuscular vaccination, Ag interaction occurs at the level of the skin epidermis (A). Then, the antigen is taken up by Langerhans dendritic cells, which migrate to nearby axial or cervical lymph nodes to activate naive T cells, resulting in the production of cytokines and chemokines, expression of co-stimulatory molecules, all of which will influence the nature and magnitude of the innate, secondary antibody responses (IgG, IgA), and peripheral CD4+T cell immune responses. The mucosal immune system includes the inductive sites, Peyer’s patches, mesenteric lymph nodes in GALT (small intestine) or lymphoid follicle-associated in BALT (bronchial-alveolar), and the effector sites (lamina propia) (B,C). In mucosal vaccination (oral, nasal), two main outcomes are possible: a mucosal and a systemic immune response leading to activation and differentiation into different CD4+, CD8+ T cells, and B cell subsets (B,C). The induction of cytokines, chemokines, and the expression of homing receptors populate the effector sites (lamina propia) in the different mucosal tissues (common mucous system), resulting in a long-lasting protective memory immune response. The induction of antibodies with enhanced functional properties (neutralizing and memory) as secretory IgA (sIgA). Cytokines such as TGF-β promote isotype switching of IgG class antibodies. Cytokines such as IL10 and IL-17 maintain homeostasis of the host response.

Figure 3

Vaccine induced protective and memory immune responses. Vaccines mimic the pathogen-induced immune response when administered by the systemic or mucosal route. In subcutaneous/intramuscular vaccination, Ag interaction occurs at the level of the skin epidermis (A). Then, the antigen is taken up by Langerhans dendritic cells, which migrate to nearby axial or cervical lymph nodes to activate naive T cells, resulting in the production of cytokines and chemokines, expression of co-stimulatory molecules, all of which will influence the nature and magnitude of the innate, secondary antibody responses (IgG, IgA), and peripheral CD4+T cell immune responses. The mucosal immune system includes the inductive sites, Peyer’s patches, mesenteric lymph nodes in GALT (small intestine) or lymphoid follicle-associated in BALT (bronchial-alveolar), and the effector sites (lamina propia) (B,C). In mucosal vaccination (oral, nasal), two main outcomes are possible: a mucosal and a systemic immune response leading to activation and differentiation into different CD4+, CD8+ T cells, and B cell subsets (B,C). The induction of cytokines, chemokines, and the expression of homing receptors populate the effector sites (lamina propia) in the different mucosal tissues (common mucous system), resulting in a long-lasting protective memory immune response. The induction of antibodies with enhanced functional properties (neutralizing and memory) as secretory IgA (sIgA). Cytokines such as TGF-β promote isotype switching of IgG class antibodies. Cytokines such as IL10 and IL-17 maintain homeostasis of the host response.