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

Figures & data

Table 1. Levels of antigen-specific IgA antibody responses at systemic and mucosal sites.

	Gastrointestinal Tract			Respiratory Tract		Reproductive Tract
Delivery route	Saliva	Intestine	Feces	Upper	Lower	Vagina	Uterus	Serum
i.p.	−(21,23,24,26) + (16,20)	++ (18,20,26)	+ (26) ++(28) +++ (27)		−(18,20,21,24,25) +(26) ++(27) +++(17)	+(18,26,28) ++(20)	+++(27)	−(27,28) +(18,23)
i.m.	+(33) ++(35)	++(47)	+(37) ++(32,47)	−(55) ++(34,35) +++(38)	−(30,38,41,50) +(36,47,49) ++(34)	+(31)		−(34) +(31,36,37) ++(47) +++(38)
s.c.	++(68)	+(59) ++(58) +++(61)	−(64,65,66) +(68)	++(60)	−(56,57,63,67)	−(62) +(68) ++(59)		−(57,62,63,66,67) ++(59,60,68) +++(61)
i.d.			−(76,77,78) +++(72)	−(79)	−(76,77) ++(69,71)	++(70,73)	+++(72)	−(76,78) +(73,77) ++(74)
TC	+(86) ++(97)	+(88) ++(86)	−(90) +(88) ++(80,81,97)	+(86)	+(83)	+(85,97) ++(86)		−(90) +(84,88,97) ++(80,82)

Levels were scored as none (−), slight (+), moderate (++), or strong (+++) based on the primary publication. The numbers in the parenthesis refer to the citations in the References.

Table 2. Levels of antigen-specific IgG antibody responses at systemic and mucosal sites.

	Gastrointestinal Tract			Respiratory Tract		Reproductive Tract
Delivery route	Saliva	Intestine	Feces	Upper	Lower	Vagina	Uterus	Serum
i.p.	+(20,23)	++(18) +++(20)	+++(27,28)		++(18,20,27)	+(18,28) ++(20)	++(27)	+(23) ++(25) +++(16-21,24-28)
i.m.	+(33)			−(38)	++(30) +++(38)	+(31) +++(39)	+(40) +++(39)	+(36)++(30,52) +++(31-35,37-39,41)
s.c.	++(68)	+(59)	+(68)	+++(60)	++(56,57) +++(63,67)	+(62,68) ++(59)		++(61,62,68) +++(57,59,60,63-67)
i.d.			++(72)		++(76) +++(75)	+(73,76)	+++(72)	−(76,78) +(73,77) ++(74)+++(75)
TC	++(86) +++(97)	+++(86)	++(97) +++(80)		+++(80) ++(83)	+(85) +++(86,97)		++(90) +++(80,81,83-85,86,88,97)

Levels were scored as none (−), slight (+), moderate (++), or strong (+++) based on the primary publication. The numbers in the parenthesis refer to the citations in the References.

Table 3. Levels of antigen-specific IgM antibody responses at systemic and mucosal sites.

	Gastrointestinal Tract			Respiratory Tract		Reproductive Tract
Delivery route	Saliva	Intestine	Feces	Upper	Lower	Vagina	Uterus	Serum
i.p.		++(18)			+++(18)	++(18)		++(18)
i.m.					+(49)			++(34,41)
s.c.								++(61)
i.d.						++(73)		+(73)++(69)
TC								-(80)+++(82)

Levels were scored as none (−), slight (+), moderate (++), or strong (+++) based on the primary publication. The numbers in the parenthesis refer to the citations in the References.

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.