Intestinal Immunoglobulin A Response to Naturally Acquired Enterotoxigenic Escherichia coli in US Travelers to an Endemic Area of Mexico

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) strains expressing only coli surface antigen 6 (CS6) have previously been isolated from patients with diarrhea, but the immunogenicity of CS6 has not been established in humans. We have detected CS6-specific immunoglobulin A responses in the feces and blood of patients convalescing from natural ETEC disease and of volunteers given an oral ETEC vaccine.

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Oral Immunization with a Salmonella typhimurium Vaccine Vector Expressing Recombinant Enterotoxigenic Escherichia coli K99 Fimbriae Elicits Elevated Antibody Titers for Protective Immunity

Infection and Immunity ◽

10.1128/iai.66.11.5470-5476.1998 ◽

1998 ◽

Vol 66 (11) ◽

pp. 5470-5476 ◽

Cited By ~ 50

Author(s):

Miguel A. Ascón ◽

David M. Hone ◽

Nancy Walters ◽

David W. Pascual

Keyword(s):

Escherichia Coli ◽

Salmonella Typhimurium ◽

Protective Immunity ◽

Mononuclear Cells ◽

Immunoglobulin A ◽

Oral Immunization ◽

Enterotoxigenic Escherichia Coli ◽

Effective Vaccine ◽

Antibody Titers ◽

And Control

ABSTRACT Bovine enterotoxigenic Escherichia coli (ETEC) continues to cause mortality in piglets and newborn calves. In an effort to develop a safe and effective vaccine for the prevention of F5+ ETEC infections, a balanced lethalasd + plasmid carrying the complete K99 operon was constructed and designated pMAK99-asd +. Introduction of this plasmid into an attenuated Salmonella typhimurium Δaro Δasd strain, H683, resulted in strain AP112, which stably expresses E. coli K99 fimbriae. A single oral immunization of BALB/c and CD-1 mice with strain AP112 elicited significant mucosal immunoglobulin A (IgA) titers that remained elevated for >11 weeks. IgA and IgG responses in serum specific for K99 fimbriae were also induced, with a prominent IgG1, as well as IgG2a and IgG2b, titer. To assess the derivation of these antibodies, a K99 isotype-specific B-cell ELISPOT analysis was conducted by using mononuclear cells from the lamina propria of the small intestines (LP), Peyer’s patches (PP), and spleens of vaccinated and control BALB/c mice. This analysis revealed elevated numbers of K99 fimbria-specific IgA-producing cells in the LP, PP, and spleen, whereas elevated K99 fimbria-specific IgG-producing cells were detected only in the PP and spleen. These antibodies were important for protective immunity. One-day-old neonates from dams orally immunized with AP112 were provided passive protection against oral challenge with wild-type ETEC, in contrast to challenged neonates from unvaccinated dams or from dams vaccinated with a control Salmonella vector. These results confirm that oral Salmonella vaccine vectors effectively deliver K99 fimbriae to mucosal inductive sites for sustained elevation of IgA and IgG antibodies and for eliciting protective immunity.

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Local and Systemic Antibody Responses to Naturally Acquired Enterotoxigenic Escherichia coli Diarrhea in an Endemic Area

The Journal of Infectious Diseases ◽

10.1093/infdis/153.3.527 ◽

1986 ◽

Vol 153 (3) ◽

pp. 527-534 ◽

Cited By ~ 43

Author(s):

B. J. Stoll ◽

A.-M. Svennerholm ◽

L. Gothefors ◽

D. Barua ◽

S. Huda ◽

...

Keyword(s):

Escherichia Coli ◽

Endemic Area ◽

Antibody Responses ◽

Enterotoxigenic Escherichia Coli

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Modulation of murine Peyer's patch immunoglobulin A response by enterotoxigenic Escherichia coli.

Infection and Immunity ◽

10.1128/iai.55.5.1085-1089.1987 ◽

1987 ◽

Vol 55 (5) ◽

pp. 1085-1089 ◽

Cited By ~ 1

Author(s):

J A Wess ◽

T M Petro

Keyword(s):

Escherichia Coli ◽

Immunoglobulin A ◽

Enterotoxigenic Escherichia Coli ◽

Peyer’S Patch ◽

Peyer's Patch

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Intestinal Immune Responses to an Inactivated Oral Enterotoxigenic Escherichia coli Vaccine and Associated Immunoglobulin A Responses in Blood

Infection and Immunity ◽

10.1128/iai.66.7.3311-3316.1998 ◽

1998 ◽

Vol 66 (7) ◽

pp. 3311-3316 ◽

Cited By ~ 76

Author(s):

Christina Åhrén ◽

Marianne Jertborn ◽

Ann-Mari Svennerholm

Keyword(s):

Escherichia Coli ◽

Immune Responses ◽

Serum Antibody ◽

Immunoglobulin A ◽

Lavage Fluid ◽

Antibody Responses ◽

Enterotoxigenic Escherichia Coli ◽

Antibody Secreting Cell ◽

Colonization Factor ◽

Iga Antibody

ABSTRACT An inactivated oral enterotoxigenic Escherichia coli(ETEC) vaccine against ETEC diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage fluid to CTB and CFAs were determined and compared with corresponding responses in stool extracts and serum as well as with IgA antibody-secreting cell (ASC) responses in peripheral blood. Two doses of vaccine induced significant IgA responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and in stool in 38 to 81% of them. The most frequent responses were seen against CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool correlated significantly (CTB,P < 0.01; CFA/I, P < 0.05) with those in intestinal lavage. Intestinal lavage responses against CFAs were best reflected by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%, followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7 to 65%) analyses. CTB-specific immune responses were seen in >90% of the vaccinees in all assays.

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Comparative Safety and Immunogenicity of Two Attenuated Enterotoxigenic Escherichia coli Vaccine Strains in Healthy Adults

Infection and Immunity ◽

10.1128/iai.74.2.994-1000.2006 ◽

2006 ◽

Vol 74 (2) ◽

pp. 994-1000 ◽

Cited By ~ 27

Author(s):

Robin McKenzie ◽

A. Louis Bourgeois ◽

Fayette Engstrom ◽

Eric Hall ◽

H. Sunny Chang ◽

...

Keyword(s):

Escherichia Coli ◽

Controlled Trial ◽

Serum Antibody ◽

Immunoglobulin A ◽

Response Rates ◽

Enterotoxigenic Escherichia Coli ◽

Enzyme Linked Immunosorbent Assay ◽

Double Blind ◽

Time Resolved ◽

Colonization Factor

ABSTRACTA vaccine against enterotoxigenicEscherichia coli(ETEC) is needed to prevent diarrheal illness among children in developing countries and at-risk travelers. Two live attenuated ETEC strains, PTL002 and PTL003, which express the ETEC colonization factor CFA/II, were evaluated for safety and immunogenicity. In a randomized, double-blind, placebo-controlled trial, 19 subjects ingested one dose, and 21 subjects ingested two doses (days 0 and 10) of PTL-002 or PTL-003 at 2 × 109CFU/dose. Anti-CFA/II mucosal immune responses were determined from the number of antibody-secreting cells (ASC) in blood measured by enzyme-linked immunospot assay, the antibody in lymphocyte supernatants (ALS) measured by enzyme-linked immunosorbent assay (ELISA), and fecal immunoglobulin A (IgA) levels determined by ELISA. Time-resolved fluorescence (TRF) ELISA was more sensitive than standard colorimetric ELISA for measuring serum antibody responses to CFA/II and its components, CS1 and CS3. Both constructs were well tolerated. Mild diarrhea occurred after 2 of 31 doses (6%) of PTL-003. PTL-003 produced more sustained intestinal colonization than PTL-002 and better IgA response rates: 90% versus 55% (P= 0.01) for anti-CFA/II IgA-ASCs, 55% versus 30% (P= 0.11) for serum anti-CS1 IgA by TRF, and 65% versus 25% (P= 0.03) for serum anti-CS3 IgA by TRF. Serum IgG response rates to CS1 or CS3 were 55% in PTL-003 recipients and 15% in PTL-002 recipients (P = 0.02). Two doses of either strain were not significantly more immunogenic than one. Based on its superior immunogenicity, which was comparable to that of a virulent ETEC strain and other ETEC vaccine candidates, PTL-003 will be developed further as a component of a live, oral attenuated ETEC vaccine.

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Enterotoxigenic Escherichia coli is detectable in water samples from an endemic area by real-time PCR

Journal of Applied Microbiology ◽

10.1111/j.1365-2672.2007.03628.x ◽

2008 ◽

Vol 104 (4) ◽

pp. 1128-1136 ◽

Cited By ~ 38

Author(s):

Å. Lothigius ◽

A. Janzon ◽

Y. Begum ◽

Å. Sjöling ◽

F. Qadri ◽

...

Keyword(s):

Escherichia Coli ◽

Real Time ◽

Water Samples ◽

Real Time Pcr ◽

Endemic Area ◽

Enterotoxigenic Escherichia Coli

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Immune Response, Ciprofloxacin Activity, and Gender Differences after Human Experimental Challenge by Two Strains of Enterotoxigenic Escherichia coli

Infection and Immunity ◽

10.1128/iai.01131-06 ◽

2006 ◽

Vol 75 (1) ◽

pp. 252-259 ◽

Cited By ~ 28

Author(s):

T. S. Coster ◽

M. K. Wolf ◽

E. R. Hall ◽

F. J. Cassels ◽

D. N. Taylor ◽

...

Keyword(s):

Escherichia Coli ◽

Immune Responses ◽

Immunoglobulin A ◽

Enterotoxigenic Escherichia Coli ◽

Antibody Secreting Cell ◽

E Coli ◽

Immunological Responses ◽

Colonization Factor ◽

Colonization Factors ◽

Colonization Factor Antigen I

ABSTRACT In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-induced diarrhea, challenge models are needed. In this study we compared clinical and immunological responses after North American volunteers were orally challenged by two ETEC strains. Groups of approximately eight volunteers received 109 or 1010 CFU of E. coli B7A (LT+ ST+ CS6+) or 108 or 109 CFU of E. coli H10407 (LT+ ST+ CFA/I+). About 75% of the volunteers developed diarrhea after challenge with 1010 CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P = 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P = 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin (LT) were measured. The responses to CFA/I were the most robust responses; all volunteers who received H10407 had serum immunoglobulin A (IgA) and IgG responses, and all but one volunteer had antibody-secreting cell (ASC) responses. One-half the volunteers who received B7A had an ASC response to CS6, and about one-third had serum IgA or IgG responses. Despite the differences in clinical illness and immune responses to colonization factors, the immune responses to LT were similar in all groups and were intermediate between the CFA/I and CS6 responses. These results provide standards for immune responses after ETEC vaccination.

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Dose-Dependent Circulating Immunoglobulin A Antibody-Secreting Cell and Serum Antibody Responses in Swedish Volunteers to an Oral Inactivated Enterotoxigenic Escherichia coli Vaccine

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.2.424-428.2001 ◽

2001 ◽

Vol 8 (2) ◽

pp. 424-428 ◽

Cited By ~ 20

Author(s):

Marianne Jertborn ◽

Christina Åhrén ◽

Ann-Mari Svennerholm

Keyword(s):

Escherichia Coli ◽

Serum Antibody ◽

Immunoglobulin A ◽

Enterotoxigenic Escherichia Coli ◽

Cholera Toxin B Subunit ◽

Secreting Cell ◽

Antibody Secreting Cell ◽

B Subunit ◽

Colonization Factor ◽

Iga Antibody

ABSTRACT The immunogenicity of different preparations of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish volunteers previously unexposed to ETEC infection. The vaccine preparations consisted of recombinant cholera toxin B subunit (CTB) and various amounts of formalin-killed whole bacteria expressing the most prevalent colonization factor antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting cell (ASC) responses against CTB and the various CFA components were seen in a majority of volunteers after two doses of ETEC vaccine independent of the vaccine lot given. The IgA ASC responses against CTB were significantly higher after the second than after the first immunization, whereas the CFA-specific IgA ASC responses were almost comparable after the first and second doses of ETEC vaccine. Two immunizations with one-third of a full dose of CFA-ETEC bacteria induced lower frequencies of IgA ASC responses against all the different CFAs than two full vaccine doses, i.e., 63 versus 80% for CFA/I, 56 versus 70% for CS1, 31 versus 65% for CS2, and 56 versus 75% for CS4. The proportion of vaccinees responding with rises in the titer of serum IgA antibody against the various CFA antigens was also lower after immunization with the reduced dose of CFA-ETEC bacteria. These findings suggest that measurements of circulating IgA ASCs can be used not only for qualitative but also for quantitative assessments of the immunogenicity of individual fimbrial antigens in various preparations of ETEC vaccine.

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