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PLoS Negl Trop Dis. 2014 Feb 6;8(2):e2683. doi: 10.1371/journal.pntd.0002683. eCollection 2014 Feb.

Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide.

Author information

1
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
2
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
3
NIDDK, LBC, National Institutes of Health, Bethesda, Maryland, United States of America.
4
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
5
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
6
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
7
Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
8
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
9
International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
10
CBER, FDA, Laboratory of Bacterial Toxins, Bethesda, Maryland, United States of America.
11
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.

Abstract

BACKGROUND:

Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children.

METHODOLOGY:

Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli.

PRINCIPAL FINDINGS:

We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model.

CONCLUSION:

We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.

PMID:
24516685
PMCID:
PMC3916310
DOI:
10.1371/journal.pntd.0002683
[Indexed for MEDLINE]
Free PMC Article

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