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PLoS Negl Trop Dis. 2015 Jul 8;9(7):e0003881. doi: 10.1371/journal.pntd.0003881. eCollection 2015.

A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

Author information

1
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
2
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
3
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), Laboratory of Bioorganic Chemistry (LBC), National Institutes of Health, Bethesda, Maryland, United States of America.
4
Harvard Medical School, Boston, Massachusetts, United States of America.
5
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts, United States of America.
6
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Division of Infectious Disease, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
7
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.
8
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
9
Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
10
Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (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; Harvard Medical School, Boston, Massachusetts, United States of America; Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, Massachusetts, United States of America.

Abstract

BACKGROUND:

Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).

METHODOLOGY:

Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.

PRINCIPLE FINDINGS:

Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.

CONCLUSION:

We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

PMID:
26154421
PMCID:
PMC4495926
DOI:
10.1371/journal.pntd.0003881
[Indexed for MEDLINE]
Free PMC Article

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