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programs, and a push for the development of vaccines against ETEC and
Shigella
is underway. Natural progression would put forward EPEC as
the next prioritized pathogen for vaccine development in pediatric dis-
ease. Early efforts using killed bacteria exhibited some efficacy (
Kubinyi
et al., 1974
). Expression of an EPEC antigen by a bacterial vector and
the elicitation of a sustained humoral response was described using bund-
lin as an antigenic component (
Schriefer et al., 1999
). Vaccines against
O-antigens have also been described, with rabbits immunized with capsu-
lated EHEC O111ac:H
-
generating antibodies that reacted against all O111
E. coli
tested, including EPEC (
Santos et al., 2010
). More recent projects
have focused on the immunogenicity of intimin. Mice immunized with
L. casei
expressing the C-terminal fragment the β-intimin required for Tir
binding generated specific antibodies that reacted against native intimin
on the surface of EPEC and inhibited EPEC attachment to epithelial cells
(
Ferreira et al., 2008
). In addition, C3H/HePas mice (a strain highly suscepti-
ble to
C. rodentium
infection) displayed significantly reduced mortality when
immunized with the same recombinant
L. casei
prior to
C. rodentium
infection
(
Ferreira et al., 2011
). The delivery of intimin protein via a
Vibrio cholerae
vector in a rabbit model further corroborates the use of this antigen. Rabbits
immunized with this strain and infected with rabbit EPEC exhibited milder
diarrhea, reduced weight loss, and reduced colonization by the pathogen
(
Keller et al., 2010
). In addition, a chitosan nanoparticle packed with por-
cine IL-4 and IL-6 has been identified as a promising adjuvant, increasing
the concentration and specificity of antibodies in the sera of mice vaccinated
against
E. coli
, and this was shown to be protective against EPEC (
Zhang
et al., 2007
).
Protective effects of breastfeeding
Numerous studies have reported the protective effects of breast-feeding.
IgA, IgM, and IgG are found in mothers' colostrum, with secretory IgA
most associated with EPEC prevention (
Araujo et al., 2005
). IgA specific
to bundlin, intimin, EspA, EspB, EspC, EspF, Tir, and other EPEC proteins
have been described (
Cravioto et al., 1991
;
Adu-Bobie et al., 1998
;
Loureiro
et al., 1998
;
Manjarrez-Hernandez et al., 2000
;
Parissi-Crivelli et al., 2000
;
Sanches et al., 2000
). Antibody levels are highest in colostrum and decrease
during lactation (
Araujo et al., 2005
). Severe morbidity and mortality are
most often associated with non-breastfed or partially breastfed infants, and a
decreasing odds ratio of dehydration is observed (
Creek et al., 2010
;
Barletta
et al., 2011
). Other components of milk, notably oligosaccharides, are also
capable of inhibiting or modifying EPEC adherence (
Cravioto et al., 1991
;
Jagannatha et al., 1991
;
Idota and Kawakami, 1995
). These findings sup-
port the importance of breast-feeding as an essential prophylactic measure in
EPEC-endemic areas.
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