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Induction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants

We tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolys... Full description

Journal Title: Vaccine 2022, Vol.40 (2), p.380-389
Main Author: Svennerholm, Ann-Mari
Other Authors: Qadri, Firdausi , Lundgren, Anna , Kaim, Joanna , Rahman Bhuiyan, Taufiqur , Akhtar, Marjahan , Maier, Nicole , Louis Bourgeois, A , Walker, Richard I
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
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title: Induction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants
format: Article
creator:
  • Svennerholm, Ann-Mari
  • Qadri, Firdausi
  • Lundgren, Anna
  • Kaim, Joanna
  • Rahman Bhuiyan, Taufiqur
  • Akhtar, Marjahan
  • Maier, Nicole
  • Louis Bourgeois, A
  • Walker, Richard I
subjects:
  • Adolescent
  • Age groups
  • ALS IgA
  • Antibodies
  • Antibodies, Bacterial
  • Antibody Formation
  • antibody-secreting cell
  • Antigens
  • Bacteria
  • Bacterial antigens
  • Child
  • Children
  • Cholera
  • Colonization
  • Contamination
  • Deactivation
  • E coli
  • Enterotoxigenic Escherichia coli
  • epidemiology
  • Escherichia coli
  • Escherichia coli Infections
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • ETEC vaccine
  • factor
  • Fecal secretory IgA
  • Feces
  • Humans
  • Immune response
  • Immunization
  • immunogenicity
  • Immunoglobulin A
  • Immunologi inom det medicinska området
  • Immunology
  • Immunology in the medical area
  • Infant
  • Infants
  • kinetics
  • Lipopolysaccharides
  • Lymphocytes
  • Medical research
  • Medicine, Experimental
  • Mucosal immunity
  • O78 LPS
  • Pathogens
  • Plasma
  • Plasma IgA
  • Plasma IgA antibodies
  • Proteins
  • Research & Experimental Medicine
  • Toxins
  • Vaccines
  • Vaccines, Inactivated
ispartof: Vaccine, 2022, Vol.40 (2), p.380-389
description: We tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolysaccharide (LPS) expressed on the vaccine strains. The vaccine was given ± double-mutant heat-labile toxin (dmLT) adjuvant. We evaluated the impact of dmLT on anti-O78 LPS immune responses and whether such responses can predict responses against the CFs as a marker for vaccine “take”. Two fractionated doses of ETVAX ± different amounts of dmLT were administered biweekly to groups of children 24–59 (n = 125), 12–23 (n = 97) and 6–11 (n = 158) months of age. Immune responses were evaluated in antibody in lymphocyte supernatants (ALS), fecal extracts and plasma. ALS IgA responses against O78 LPS were induced in 44–49% of the children aged 12–59 months. The magnitudes of the ALS responses were significantly higher in children receiving a half-dose (5 × 1010 bacteria) of ETVAX ± dmLT than in placebo recipients.
language: eng
source:
identifier: ISSN: 0264-410X
fulltext: no_fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleInduction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants
creatorSvennerholm, Ann-Mari ; Qadri, Firdausi ; Lundgren, Anna ; Kaim, Joanna ; Rahman Bhuiyan, Taufiqur ; Akhtar, Marjahan ; Maier, Nicole ; Louis Bourgeois, A ; Walker, Richard I
creatorcontribSvennerholm, Ann-Mari ; Qadri, Firdausi ; Lundgren, Anna ; Kaim, Joanna ; Rahman Bhuiyan, Taufiqur ; Akhtar, Marjahan ; Maier, Nicole ; Louis Bourgeois, A ; Walker, Richard I ; Sahlgrenska akademin ; Institute of Biomedicine, Department of Microbiology and Immunology ; Göteborgs universitet ; Gothenburg University ; Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi ; Sahlgrenska Academy
descriptionWe tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolysaccharide (LPS) expressed on the vaccine strains. The vaccine was given ± double-mutant heat-labile toxin (dmLT) adjuvant. We evaluated the impact of dmLT on anti-O78 LPS immune responses and whether such responses can predict responses against the CFs as a marker for vaccine “take”. Two fractionated doses of ETVAX ± different amounts of dmLT were administered biweekly to groups of children 24–59 (n = 125), 12–23 (n = 97) and 6–11 (n = 158) months of age. Immune responses were evaluated in antibody in lymphocyte supernatants (ALS), fecal extracts and plasma. ALS IgA responses against O78 LPS were induced in 44–49% of the children aged 12–59 months. The magnitudes of the ALS responses were significantly higher in children receiving a half-dose (5 × 1010 bacteria) of ETVAX ± dmLT than in placebo recipients. <10% of the vaccinees aged 6–11 months mounted ALS responses against O78 LPS. However, 49% of the infants developed fecal secretory IgA responses which were significantly more frequent in those receiving a quarter-dose (2.5 × 1010 bacteria) of vaccine + dmLT (62%) compared to a quarter-dose alone (36%). Plasma IgA antibody responses were induced in 80% of older children and 36% of infants. The frequencies of O78 LPS responses in plasma and feces were comparable or higher than against the vaccine CFs in infants. Our findings show that ETVAX induced mucosal and systemic immune responses against O78 LPS in all age groups and that dmLT improved intestinal immune responses among infants. These observations may have implications for more successful use of other oral vaccines based on O antigens in children.
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1EISSN: 1873-2518
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languageeng
publisherNetherlands: Elsevier Ltd
subjectAdolescent ; Age groups ; ALS IgA ; Antibodies ; Antibodies, Bacterial ; Antibody Formation ; antibody-secreting cell ; Antigens ; Bacteria ; Bacterial antigens ; Child ; Children ; Cholera ; Colonization ; Contamination ; Deactivation ; E coli ; Enterotoxigenic Escherichia coli ; epidemiology ; Escherichia coli ; Escherichia coli Infections ; Escherichia coli Proteins ; Escherichia coli Vaccines ; ETEC vaccine ; factor ; Fecal secretory IgA ; Feces ; Humans ; Immune response ; Immunization ; immunogenicity ; Immunoglobulin A ; Immunologi inom det medicinska området ; Immunology ; Immunology in the medical area ; Infant ; Infants ; kinetics ; Lipopolysaccharides ; Lymphocytes ; Medical research ; Medicine, Experimental ; Mucosal immunity ; O78 LPS ; Pathogens ; Plasma ; Plasma IgA ; Plasma IgA antibodies ; Proteins ; Research & Experimental Medicine ; Toxins ; Vaccines ; Vaccines, Inactivated
ispartofVaccine, 2022, Vol.40 (2), p.380-389
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02022 University of Gothenburg, Sweden
1Copyright © 2021. Published by Elsevier Ltd.
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0Svennerholm, Ann-Mari
1Qadri, Firdausi
2Lundgren, Anna
3Kaim, Joanna
4Rahman Bhuiyan, Taufiqur
5Akhtar, Marjahan
6Maier, Nicole
7Louis Bourgeois, A
8Walker, Richard I
9Sahlgrenska akademin
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11Göteborgs universitet
12Gothenburg University
13Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
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0Induction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants
1Vaccine
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descriptionWe tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolysaccharide (LPS) expressed on the vaccine strains. The vaccine was given ± double-mutant heat-labile toxin (dmLT) adjuvant. We evaluated the impact of dmLT on anti-O78 LPS immune responses and whether such responses can predict responses against the CFs as a marker for vaccine “take”. Two fractionated doses of ETVAX ± different amounts of dmLT were administered biweekly to groups of children 24–59 (n = 125), 12–23 (n = 97) and 6–11 (n = 158) months of age. Immune responses were evaluated in antibody in lymphocyte supernatants (ALS), fecal extracts and plasma. ALS IgA responses against O78 LPS were induced in 44–49% of the children aged 12–59 months. The magnitudes of the ALS responses were significantly higher in children receiving a half-dose (5 × 1010 bacteria) of ETVAX ± dmLT than in placebo recipients. <10% of the vaccinees aged 6–11 months mounted ALS responses against O78 LPS. However, 49% of the infants developed fecal secretory IgA responses which were significantly more frequent in those receiving a quarter-dose (2.5 × 1010 bacteria) of vaccine + dmLT (62%) compared to a quarter-dose alone (36%). Plasma IgA antibody responses were induced in 80% of older children and 36% of infants. The frequencies of O78 LPS responses in plasma and feces were comparable or higher than against the vaccine CFs in infants. Our findings show that ETVAX induced mucosal and systemic immune responses against O78 LPS in all age groups and that dmLT improved intestinal immune responses among infants. These observations may have implications for more successful use of other oral vaccines based on O antigens in children.
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1Age groups
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3Antibodies
4Antibodies, Bacterial
5Antibody Formation
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7Antigens
8Bacteria
9Bacterial antigens
10Child
11Children
12Cholera
13Colonization
14Contamination
15Deactivation
16E coli
17Enterotoxigenic Escherichia coli
18epidemiology
19Escherichia coli
20Escherichia coli Infections
21Escherichia coli Proteins
22Escherichia coli Vaccines
23ETEC vaccine
24factor
25Fecal secretory IgA
26Feces
27Humans
28Immune response
29Immunization
30immunogenicity
31Immunoglobulin A
32Immunologi inom det medicinska området
33Immunology
34Immunology in the medical area
35Infant
36Infants
37kinetics
38Lipopolysaccharides
39Lymphocytes
40Medical research
41Medicine, Experimental
42Mucosal immunity
43O78 LPS
44Pathogens
45Plasma
46Plasma IgA
47Plasma IgA antibodies
48Proteins
49Research & Experimental Medicine
50Toxins
51Vaccines
52Vaccines, Inactivated
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titleInduction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants
authorSvennerholm, Ann-Mari ; Qadri, Firdausi ; Lundgren, Anna ; Kaim, Joanna ; Rahman Bhuiyan, Taufiqur ; Akhtar, Marjahan ; Maier, Nicole ; Louis Bourgeois, A ; Walker, Richard I
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2ALS IgA
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4Antibodies, Bacterial
5Antibody Formation
6antibody-secreting cell
7Antigens
8Bacteria
9Bacterial antigens
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13Colonization
14Contamination
15Deactivation
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29Immunization
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31Immunoglobulin A
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34Immunology in the medical area
35Infant
36Infants
37kinetics
38Lipopolysaccharides
39Lymphocytes
40Medical research
41Medicine, Experimental
42Mucosal immunity
43O78 LPS
44Pathogens
45Plasma
46Plasma IgA
47Plasma IgA antibodies
48Proteins
49Research & Experimental Medicine
50Toxins
51Vaccines
52Vaccines, Inactivated
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1Qadri, Firdausi
2Lundgren, Anna
3Kaim, Joanna
4Rahman Bhuiyan, Taufiqur
5Akhtar, Marjahan
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7Louis Bourgeois, A
8Walker, Richard I
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12Gothenburg University
13Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
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abstractWe tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolysaccharide (LPS) expressed on the vaccine strains. The vaccine was given ± double-mutant heat-labile toxin (dmLT) adjuvant. We evaluated the impact of dmLT on anti-O78 LPS immune responses and whether such responses can predict responses against the CFs as a marker for vaccine “take”. Two fractionated doses of ETVAX ± different amounts of dmLT were administered biweekly to groups of children 24–59 (n = 125), 12–23 (n = 97) and 6–11 (n = 158) months of age. Immune responses were evaluated in antibody in lymphocyte supernatants (ALS), fecal extracts and plasma. ALS IgA responses against O78 LPS were induced in 44–49% of the children aged 12–59 months. The magnitudes of the ALS responses were significantly higher in children receiving a half-dose (5 × 1010 bacteria) of ETVAX ± dmLT than in placebo recipients. <10% of the vaccinees aged 6–11 months mounted ALS responses against O78 LPS. However, 49% of the infants developed fecal secretory IgA responses which were significantly more frequent in those receiving a quarter-dose (2.5 × 1010 bacteria) of vaccine + dmLT (62%) compared to a quarter-dose alone (36%). Plasma IgA antibody responses were induced in 80% of older children and 36% of infants. The frequencies of O78 LPS responses in plasma and feces were comparable or higher than against the vaccine CFs in infants. Our findings show that ETVAX induced mucosal and systemic immune responses against O78 LPS in all age groups and that dmLT improved intestinal immune responses among infants. These observations may have implications for more successful use of other oral vaccines based on O antigens in children.
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pubElsevier Ltd
pmid34772542
doi10.1016/j.vaccine.2021.10.056
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