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PLoS Negl Trop Dis. 2019 Nov 19;13(11):e0007874. doi: 10.1371/journal.pntd.0007874. eCollection 2019 Nov.

Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba.

Author information

1
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
2
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
3
Harvard Medical School, Boston, Massachusetts, United States of America.
4
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), Laboratory of Bioorganic Chemistry (LBC), National Institutes of Health, Bethesda, Maryland, United States of America.
5
Merck & Co., Inc., Kenilworth, New Jersey, United States of America.
6
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
7
PaxVax, Inc., Redwood City, California, United States of America.
8
Vaccine Testing Center, Departments of Medicine and Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
9
Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
10
Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
11
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
12
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
13
Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Abstract

BACKGROUND:

Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans.

METHODOLOGY:

We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera.

PRINCIPAL FINDINGS:

We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter.

CONCLUSIONS:

Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations.

TRIAL REGISTRATION NUMBER:

ClinicalTrials.gov NCT01895855.

PMID:
31743334
DOI:
10.1371/journal.pntd.0007874
Free PMC Article

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jakub K. Simon, Michael Lock, and Marc Gurwith were employed by PaxVax, Inc. Wilbur H. Chen, Caroline E. Lyon, Beth D. Kirkpatrick, Mitchell Cohen, and Myron M. Levine received research funding from PaxVax, Inc. Jakub K. Simon is currently employed by Merck & Co. All other authors report no potential conflicts.

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