scholarly journals Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139

mSphere ◽  
2021 ◽  
Author(s):  
Mohammad Kamruzzaman ◽  
Meagan Kelly ◽  
Richelle C. Charles ◽  
Jason B. Harris ◽  
Stephen B. Calderwood ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Specific Antibody ◽  
Cholera Vaccine ◽  
Conjugate Vaccines ◽  
Content Type ◽  
Oral Cholera Vaccine ◽  
Vibrio Cholerae O139 ◽  
Specific Polysaccharide

Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against cholera is serogroup specific, and serogroup specificity is defined by O-specific polysaccharide (OSP).

scholarly journals Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

2013 ◽  
Vol 20 (6) ◽  
pp. 780-788 ◽  
Author(s):  
Daniel T. Leung ◽  
Taher Uddin ◽  
Peng Xu ◽  
Amena Aktar ◽  
Russell A. Johnson ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Cholera Vaccine ◽  
Wild Type ◽  
Older Children ◽  
Content Type ◽  
Oral Cholera Vaccine ◽  
Specific Polysaccharide

ABSTRACTCurrent oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses toVibrio choleraelipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses againstV. choleraeO-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months,n= 15), young children (24 to 59 months,n= 14), and older children (5 to 15 years,n= 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response toV. choleraeOSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-typeV. choleraeO1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.

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

2010 ◽  
Vol 59 (2) ◽  
pp. 158-164 ◽  
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.

scholarly journals 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

2012 ◽  
Vol 19 (4) ◽  
pp. 594-602 ◽  
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.

scholarly journals Randomized, Double-Blind, Placebo-Controlled, Multicentered Trial of the Efficacy of a Single Dose of Live Oral Cholera Vaccine CVD 103-HgR in Preventing Cholera following Challenge with Vibrio cholerae O1 El Tor Inaba Three Months after Vaccination

1999 ◽  
Vol 67 (12) ◽  
pp. 6341-6345 ◽  
Author(s):  
Carol O. Tacket ◽  
Mitchell B. Cohen ◽  
Steven S. Wasserman ◽  
Genevieve Losonsky ◽  
Sofie Livio ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Protective Efficacy ◽  
Mercury Resistance ◽  
Cholera Vaccine ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Oral Cholera Vaccine ◽  
K 12 ◽  
El Tor ◽  
Placebo Recipients

ABSTRACT CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 × 108to 8 × 108 CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 105 CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a ≥4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (≥3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stoolV. cholerae excretion among placebo recipients was 1.1 × 107 CFU/g and among vaccinees was 4.9 × 102 CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.

scholarly journals Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108

2003 ◽  
Vol 71 (10) ◽  
pp. 5498-5504 ◽  
Author(s):  
Weili Liang ◽  
Shixia Wang ◽  
Fenggang Yu ◽  
Lijuan Zhang ◽  
Guoming Qi ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Rabbit Model ◽  
Housekeeping Gene ◽  
Cholera Vaccine ◽  
Oral Cholera Vaccine ◽  
Toxigenic Strains ◽  
El Tor ◽  
Full Protection

ABSTRACT IEM101, a Vibrio cholerae O1 El Tor Ogawa strain naturally deficient in CTXΦ, was previously selected as a live cholera vaccine candidate. To make a better and safer vaccine that can induce protective immunity against both the bacteria and cholera toxin (CT), a new vaccine candidate, IEM108, was constructed by introducing a ctxB gene and an El Tor-derived rstR gene into IEM101. The ctxB gene codes for the protective antigen CTB subunit, and the rstR gene mediates phage immunity. The stable expression of the two genes was managed by a chromosome-plasmid lethal balanced system based on the housekeeping gene thyA. Immunization studies indicate that IEM108 generates good immune responses against both the bacteria and CT. After a single-dose intraintestinal vaccination with 109 CFU of IEM108, both anti-CTB immunoglobulin G and vibriocidal antibodies were detected in the immunized-rabbit sera. However, only vibriocidal antibodies are detected in rabbits immunized with IEM101. In addition, IEM108 but not IEM101 conferred full protection against the challenges of four wild-type toxigenic strains of V. cholerae O1 and 4 μg of CT protein in a rabbit model. By introducing the rstR gene, the frequency of conjugative transfer of a recombinant El Tor-derived RS2 suicidal plasmid to IEM108 was decreased 100-fold compared to that for IEM101. This indicated that the El Tor-derived rstR cloned in IEM108 was fully functional and could effectively inhibit the El Tor-derived CTXΦ from infecting IEM108. Our results demonstrate that IEM108 is an efficient and safe live oral cholera vaccine candidate that induces antibacterial and antitoxic immunity and CTXΦ phage immunity.

scholarly journals Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Richelle C. Charles ◽  
Meagan Kelly ◽  
Jenny M. Tam ◽  
Aklima Akter ◽  
Motaher Hossain ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Vibrio Cholerae ◽  
Polyclonal Antibody ◽  
High Speed ◽  
Intestinal Lumen ◽  
Dependent Manner ◽  
Content Type ◽  
Specific Antibodies ◽  
Specific Polysaccharide

ABSTRACT The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae correlate highly with protection against cholera. V. cholerae is highly motile and possesses a flagellum sheathed in OSP, and motility of V. cholerae correlates with virulence. Using high-speed video microscopy and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block V. cholerae motility at both subagglutinating and agglutinating concentrations. This antimotility effect is reversed by preadsorbing sera and polyclonal antibody fractions with purified OSP and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. Fab fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated cross-linking in motility inhibition. We show that OSP-specific antibodies do not directly affect V. cholerae viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used in vivo competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of V. cholerae in intestinal tissues and that this impact is motility dependent. Our findings suggest that the impedance of motility by antibodies targeting V. cholerae OSP contributes to protection against cholera. IMPORTANCE Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae. V. cholerae is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and V. cholerae motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since V. cholerae is a noninvasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit V. cholerae motility and are associated with protection against challenge in a motility-dependent manner.

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