scholarly journals Secondary Vibrio cholerae-specific cellular antibody responses following wild-type homologous challenge in people vaccinated with CVD 103-HgR live oral cholera vaccine: changes with time and lack of correlation with protection.

1993 ◽  
Vol 61 (2) ◽  
pp. 729-733 ◽  
Author(s):  
G A Losonsky ◽  
C O Tacket ◽  
S S Wasserman ◽  
J B Kaper ◽  
M M Levine
Keyword(s):  
Vibrio Cholerae ◽  
Antibody Responses ◽  
Cholera Vaccine ◽  
Wild Type ◽  
Oral Cholera Vaccine ◽  
Homologous Challenge

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 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 Safety and immunogenicity of a booster dose of Vibrio cholerae CVD 103-HgR live oral cholera vaccine in Swiss adults.

1992 ◽  
Vol 60 (9) ◽  
pp. 3916-3917 ◽  
Author(s):  
S J Cryz ◽  
M M Levine ◽  
G Losonsky ◽  
J B Kaper ◽  
B Althaus
Keyword(s):  
Vibrio Cholerae ◽  
Booster Dose ◽  
Cholera Vaccine ◽  
Oral Cholera Vaccine

scholarly journals The gut microbiota and development of Vibrio cholerae -specific long-term memory B cells in adults after whole-cell killed oral cholera vaccine

2021 ◽  
Author(s):  
Denise Chac ◽  
Taufiqur R. Bhuiyan ◽  
Amit Saha ◽  
Mohammad M. Alam ◽  
Umme Salma ◽  
...  
Keyword(s):  
B Cells ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Vibrio Cholerae ◽  
Memory B Cells ◽  
Health Concern ◽  
Cholera Vaccine ◽  
Vaccine Adjuvants ◽  
Oral Cholera Vaccine

Cholera is a diarrheal disease caused by Vibrio cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. cholerae and may be a major determinant of long-term protection from cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may “prime” the mucosal immune response to vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.

scholarly journals Non-toxigenic Vibrio cholerae challenge strains for evaluating vaccine efficacy and inferring mechanisms of protection

2021 ◽  
Author(s):  
Bolutife Fakoya ◽  
Karthik Hullahalli ◽  
Daniel H.F. Rubin ◽  
Deborah R. Leitner ◽  
Roma Chilengi ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Clinical Isolate ◽  
Vaccine Efficacy ◽  
Antibody Responses ◽  
Immune Protection ◽  
Cholera Vaccine ◽  
Intestinal Colonization ◽  
Severe Diarrhea ◽  
Primary Mechanism

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. To minimize the risk of severe diarrhea these strains were rendered non-toxigenic, since antibody responses which limit V. cholerae colonization are the primary mechanism of immune protection. These strains did not cause diarrhea in infant mice and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. They are also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination tightens the infection bottleneck without restricting pathogen expansion in vivo. ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.

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