What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?

Abstract

The route of vaccination is important in influencing immune responses at the initial site of pathogen invasion where protection is most effective. Immune responses required for mucosal protection can differ vastly depending on the individual pathogen. For some mucosal pathogens, including acute self-limiting infections, high-titer neutralizing Abs that enter tissue parenchyma or transude into the mucosal lumen are sufficient for clearing cell-free virus. However, for pathogens causing chronic infections such as HIV, hepatitis C virus, herpes viruses, mycobacteria, and fungal and parasitic infections, a single arm of the immune response generated by systemic vaccination may be insufficient for protection. Induction of the mucosal innate and adaptive immune systems, including CD4+ T help, Th17, high avidity CD8+ CTL, and secretory IgA and IgG1 neutralizing Abs, at the site of pathogen entry may be required for effective protection against highly invasive pathogens that lead to chronic infection and may be generated predominantly by mucosal vaccination.

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“…Massive depletion of CD4 1 CCR5 1 memory T cells occurs in the mucosal tissues within the first 2 weeks of HIV-1 infection [1,2]. In connection with this, vaccines providing protection against gastrointestinal infectious diseases must be able to induce long-term mucosal immune responses [3][4][5][6][7][8][9]. Previously, we demonstrated that long-lasting protection against mucosal viral transmission could be accomplished by CD8 1 CTLs that must be present at the mucosal site of antigen exposure, although some mucosal memory CTLs may be induced even after systemic vaccination [10][11][12][13][14][15][16].…”