Induction of mucosal immunity through systemic immunization: Phantom or reality?

Abstract

Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity.

Keywords: IgA; adjuvant; mucosal immunity; systemic immunization.

Figure 1.

Potential mechanisms of systemic vaccination-induced mucosal antibody responses. Intradermal (i.d.) or transcutaneous (TC) immunization activates Langerhans cells and dermal dendritic cells in the epidermis and dermis of skin, which then migrate to the mucosa-associated lymphoid tissue (MALT) where they present the antigen to CD4⁺ T cells and B cells. An antigen delivered by i.m. or s.c. route mainly diffuses to the draining peripheral lymph nodes (DPLN) where it activates APCs, such as B cells, dendritic cells and macrophages. Mucosal antibody responses are triggered when they reach to the MALT and present the antigen to CD4⁺ T cells and B cells. A free antigen may migrate to MALT directly.