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

ABSTRACTImmunity againstVibrio choleraeO1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses toV. choleraeOSP have not previously been characterized. We assessed immune responses againstV. choleraeOSP in adults with cholera caused byV. choleraeO1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core–bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R= 0.86, 0.73, and 0.91, respectively;P< 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R= 0.60, 0.60, and 0.92, respectively;P< 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R= 0.80 and 0.66, respectively;P< 0.001). Addition of either OSPc:BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targetingV. choleraeLPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targetingV. choleraeOSP.

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Vibrio cholerae O1 Ogawa detoxified lipopolysaccharide structures as inducers of cytokines and oxidative species in macrophages

Journal of Medical Microbiology ◽

10.1099/jmm.0.013599-0 ◽

2010 ◽

Vol 59 (2) ◽

pp. 158-164 ◽

Cited By ~ 8

Author(s):

Ema Paulovičová ◽

Elena Kováčová ◽

Slavomír Bystrický

Keyword(s):

Vibrio Cholerae ◽

Ex Vivo ◽

Peritoneal Macrophages ◽

Cholera Vaccine ◽

Specific Polysaccharide ◽

Vibrio Cholerae O1 ◽

Mouse Peritoneal Macrophages ◽

Oxidative Species ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Multidrug resistance in several strains of Vibrio cholerae has encouraged anti-cholera vaccine developmental attempts using various subcellular moieties. In order to examine the immunological efficacy of detoxified LPS (dLPS)-derived saccharide immunogens, ex vivo activation of mouse peritoneal macrophages (MΦs) was investigated. The immunomodulatory effect was evaluated via induction of the pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-1α and IL-6 and acceleration of nitric oxide (NO) and reactive oxygen species (ROS). Immunologically active structures triggered mouse peritoneal MΦs to secrete cytokines and release NO/ROS, even at concentrations as low as 12.5 μg ml−1. It was found that the O-specific polysaccharide moiety was more immunologically efficient than the glycolipid one, probably due to the position of 3-deoxy-d-manno-octulosonic acid. The results revealed effective structure–immunomodulating relationships of dLPS-derived moieties that are desirable in subcellular anti-cholera vaccine design.

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Synthesis and Molecular Structure of the 5-Methoxycarbonylpentyl α-Glycoside of the Upstream, Terminal Moiety of the O-Specific Polysaccharide of Vibrio cholerae O1, Serotype Inaba

Molecules ◽

10.3390/molecules20022892 ◽

2015 ◽

Vol 20 (2) ◽

pp. 2892-2902 ◽

Cited By ~ 2

Author(s):

Peng Xu ◽

Edwin Stevens ◽

Alfred French ◽

Pavol Kováč

Keyword(s):

Molecular Structure ◽

Vibrio Cholerae ◽

Specific Polysaccharide ◽

Vibrio Cholerae O1

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Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.05689-11 ◽

2012 ◽

Vol 19 (4) ◽

pp. 594-602 ◽

Cited By ~ 17

Author(s):

A. A. Tarique ◽

A. Kalsy ◽

M. Arifuzzaman ◽

S. M. Rollins ◽

R. C. Charles ◽

...

Keyword(s):

Immune Responses ◽

Vibrio Cholerae ◽

Protective Immunity ◽

Protective Efficacy ◽

Immune Serum ◽

Whole Cell ◽

Content Type ◽

Specific Polysaccharide ◽

Subcutaneous Immunization ◽

Cholera Vaccination

ABSTRACTA shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide ofVibrio choleraeO1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) orEscherichia coliheat-labile toxin (LT) following oral priming with attenuatedV. choleraeO1 vaccine strain O395-NT resulted in significant increases in serum anti-V. choleraeLPS IgG, IgM, and IgA (P< 0.01) responses as well as in anti-Ogawa (P< 0.01) and anti-Inaba (P< 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P< 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses againstV. cholerae.

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Immunological efficacy of glycoconjugates derived from Vibrio cholerae O1 serotype Ogawa detoxified LPS in mice

Journal of Medical Microbiology ◽

10.1099/jmm.0.020875-0 ◽

2010 ◽

Vol 59 (12) ◽

pp. 1440-1448 ◽

Cited By ~ 7

Author(s):

Ema Paulovičová ◽

Jana Korcová ◽

Pavol Farkaš ◽

Slavomír Bystrický

Keyword(s):

B Cell ◽

Vibrio Cholerae ◽

Primary Vaccination ◽

Receptor Expression ◽

T Helper 1 ◽

Phagocytic Capacity ◽

Humoral And Cellular Immunity ◽

Significant Acceleration ◽

Specific Polysaccharide ◽

Vibrio Cholerae O1

This study focused on changes in selected parameters of humoral and cellular immunity following vaccination of mice with unique Vibrio cholerae LPS–protein-complexed conjugates. The V. cholerae detoxified LPS (dLPS)-derived antigenic structures O-specific polysaccharide (O-SP) and de-O-acylated LPS (DeOAc-LPS) were used to prepare glycoconjugates by linking both dLPSs to glucan, the immunomodulating matrix, and then to BSA carrier. Animals were given a primary vaccination and boosted at 2-week intervals with a dose of 4.5 μg saccharide antigen. The last boost was given either subcutaneously or intraperitoneally (i.p.) to compare the boosting effect and to optimize the effective immunization route. Both conjugates (O-SP–BSA and DeOAc-LPS–BSA) induced significant levels of antigen-specific Ig isotypes, especially IgG and IgM. The i.p. booster route was more effective. A T helper 1 response was achieved only by immunization with O-SP–BSA conjugate administered i.p. Significant acceleration of phagocytic capacity and respiratory burst of neutrophils was demonstrated by both immunogenic formulations. Activation of T- and B-cell adaptive immunities was exhibited as specific changes in CD3 : CD19 and CD4 : CD8 ratios, B-cell low-affinity Fcγ II and III receptor expression and induction of CD45R antigen.

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Systemic, Mucosal, and Memory Immune Responses following Cholera

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6040192 ◽

2021 ◽

Vol 6 (4) ◽

pp. 192

Author(s):

Edward T. Ryan ◽

Daniel T. Leung ◽

Owen Jensen ◽

Ana A. Weil ◽

Taufiqur Rahman Bhuiyan ◽

...

Keyword(s):

Public Health ◽

Immune Responses ◽

Vibrio Cholerae ◽

Innate Immune ◽

Innate Immune Responses ◽

Correlates Of Protection ◽

Public Health Threat ◽

Significant Public Health ◽

Vibrio Cholerae O1 ◽

Cholera Vaccines

Vibrio cholerae O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera vaccines is the need for a better understanding of the primary mechanisms of cholera immunity and identification of improved correlates of protection. Considerable progress has been made over the last decade in understanding the adaptive and innate immune responses to cholera disease as well as V. cholerae infection. This review will assess what is currently known about the systemic, mucosal, memory, and innate immune responses to clinical cholera, as well as recent advances in our understanding of the mechanisms and correlates of protection against V. cholerae O1 infection.

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