- Introduction
- Materials and Methods
- Study population.
- Antigen preparation.
- Enzyme-linked immunosorbent assays (ELISAs) for OSP and LPS-specific Immunoglobulin A (IgA), IgG, and IgM antibodies in plasma.
- Vibriocidal antibody assay in plasma.
- Quantification of circulating IgA, IgG, and IgM ASC to OSP, LPS, and CtxB.
- ELISAs for OSP-, LPS- and CtxB-specific IgA, IgG, and IgM antibodies in supernatants of memory B-cell culture.
- Statistical analyses.
- Results
- Comparison of IgA, IgG, and IgM antibody responses in plasma to V. cholerae O1 OSP and LPS antigens in vaccinees and patients.
- Comparison of plasma antibody responses to OSP and LPS with vibriocidal antibody responses in vaccinees.
- Circulating IgA, IgG, and IgM antibody secreting cells after vaccination or infection.
- Development of memory B-cell responses as assessed in memory B-cell culture supernatants.
- Discussion
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Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera
Taher Uddin
Taher Uddin
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Amena Aktar
Amena Aktar
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Peng Xu
Peng Xu
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Russell A. Johnson
Russell A. Johnson
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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M. Arifur Rahman
M. Arifur Rahman
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Daniel T. Leung
Daniel T. Leung
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Sadia Afrin
Sadia Afrin
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Aklima Akter
Aklima Akter
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Mohammad Murshid Alam
Mohammad Murshid Alam
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Atiqur Rahman
Atiqur Rahman
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Fahima Chowdhury
Fahima Chowdhury
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Ashraful I. Khan
Ashraful I. Khan
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Taufiqur Rahman Bhuiyan
Taufiqur Rahman Bhuiyan
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Meagan K. Bufano
Meagan K. Bufano
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Rasheduzzaman Rashu
Rasheduzzaman Rashu
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Yanan Yu
Yanan Yu
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Ying Wu-Freeman
Ying Wu-Freeman
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Jason B. Harris
Jason B. Harris
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Regina C. LaRocque
Regina C. LaRocque
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Richelle C. Charles
Richelle C. Charles
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Pavol Kováč
Pavol Kováč
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Stephen B. Calderwood
Stephen B. Calderwood
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Edward T. Ryan
Edward T. Ryan
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Firdausi Qadri
Firdausi Qadri
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; NIDDK, LBC, National Institutes of Health, Bethesda, Maryland; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
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Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection.
Author Notes
Financial support: This research was supported by the icddr,b, by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S.B.C., E.T.R.], R03 AI063079 [F.Q.], U01 AI077883 and AI106878 [E.T.R.]), K08 AI089721 [R.C.C.], K08AI100923 [D.T.L.]) and the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T.U., M.M.A., R.R., and F.Q.]), Career Development Awards (K01 TW07409 [J.B.H.] and K01 TW07144 [R.C.L.], and a Fogarty International Clinical Research Scholars Award (R24 TW007988 [T.U., R.A.J.]), as well as by Swedish Sida grant INT-ICDDR,B-HN-01-AV (F.Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R.C.L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund (D.T.L.), and a Thrasher Research Fund Early Career Award (D.T.L.).
Authors' addresses: Taher Uddin, Amena Aktar, Russell A. Johnson, M. Arifur Rahman, Sadia Afrin, Aklima Akter, Mohammad Murshid Alam, Fahima Chowdhury, Ashraful I. Khan, and Firdausi Qadri, International Centre For Diarrhoeal Disease Research, Bangladesh (icddr,b) - Immunology Laboratory, Dhaka, Bangladesh, E-mails: taher_imm@icddrb.org, bio_amn015@yahoo.com, russell.a.johnson@gmail.com, marifur@icddrb.org, sadia_afrin89@yahoo.com, aklima17@gmail.com, shafiul@icddrb.org, fchowdhury@icddrb.org, ashrafk@icddrb.org, and fqadri@icddrb.org. Peng Xu and Pavol Kováč, National Institutes of Health - NIDDK, LBC, Bethesda, MD, E-mails: xup3@mail.nih.gov and Kovac@mail.nih.gov. Daniel T. Leung, Meagan K. Bufano, Yanan Yu, and Ying Wu-Freeman, Massachusetts General Hospital - Infectious Diseases, Boston, MA, E-mails: dleung@partners.org, MBUFANO@partners.org, YYVAUGHN@PARTNERS.ORG, and YWUFREEMAN@PARTNERS.ORG. Atiqur Rahman, University of Dhaka - Department of Biochemistry and Molecular Biology, Dhaka, Bangladesh, E-mail: atique303@gmail.com. Rasheduzzaman Rashu, International Centre For Diarrhoeal Disease Research, Bangladesh (icddr,b) - Immunology Laboratory, Dhaka, Bangladesh, and Massachusetts General Hospital - Infectious Diseases, Boston, MA, E-mail: rashedimm@yahoo.com. Jason B. Harris, Department of Pediatrics, Harvard Medical School, Boston, MA, and Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, E-mail: jbharris@partners.org. Regina C. LaRocque and Richelle C. Charles, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, and Department of Medicine, Harvard Medical School, Boston, MA, E-mails: RCLAROCQUE@PARTNERS.ORG and RCCHARLES@PARTNERS.ORG. Stephen Calderwood, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, Department of Medicine, Harvard Medical School, Boston, MA, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, E-mail: SCALDERWOOD@PARTNERS.ORG. Edward T. Ryan, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, Department of Medicine, Harvard Medical School, Boston, MA, and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, E-mail: ETRYAN@PARTNERS.ORG.
- Introduction
- Materials and Methods
- Study population.
- Antigen preparation.
- Enzyme-linked immunosorbent assays (ELISAs) for OSP and LPS-specific Immunoglobulin A (IgA), IgG, and IgM antibodies in plasma.
- Vibriocidal antibody assay in plasma.
- Quantification of circulating IgA, IgG, and IgM ASC to OSP, LPS, and CtxB.
- ELISAs for OSP-, LPS- and CtxB-specific IgA, IgG, and IgM antibodies in supernatants of memory B-cell culture.
- Statistical analyses.
- Results
- Comparison of IgA, IgG, and IgM antibody responses in plasma to V. cholerae O1 OSP and LPS antigens in vaccinees and patients.
- Comparison of plasma antibody responses to OSP and LPS with vibriocidal antibody responses in vaccinees.
- Circulating IgA, IgG, and IgM antibody secreting cells after vaccination or infection.
- Development of memory B-cell responses as assessed in memory B-cell culture supernatants.
- Discussion
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