Safety and Immunogenicity of Live Oral Cholera Vaccine Candidate CVD 110, a  ctxA ctxAzot zotace Derivative of El Tor Ogawa Vibrio cholerae

1993 ◽  
Vol 168 (6) ◽  
pp. 1536-1540 ◽  
Author(s):  
C. O. Tacket ◽  
G. Losonsky ◽  
J. P. Nataro ◽  
S. J. Cryz ◽  
R. Edelman ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Vaccine Candidate ◽  
Cholera Vaccine ◽  
Oral Cholera Vaccine ◽  
El Tor

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 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 Randomized, Controlled Human Challenge Study of the Safety, Immunogenicity, and Protective Efficacy of a Single Dose of Peru-15, a Live Attenuated Oral Cholera Vaccine

2002 ◽  
Vol 70 (4) ◽  
pp. 1965-1970 ◽  
Author(s):  
Mitchell B. Cohen ◽  
Ralph A. Giannella ◽  
Judy Bean ◽  
David N. Taylor ◽  
Susan Parker ◽  
...  
Keyword(s):  
Confidence Limit ◽  
Protective Efficacy ◽  
Oral Vaccine ◽  
Human Volunteer ◽  
Cholera Vaccine ◽  
Double Blind ◽  
Severe Diarrhea ◽  
Oral Cholera Vaccine ◽  
El Tor ◽  
Placebo Recipients

ABSTRACT Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model. A total of 59 volunteers were randomly allocated to groups to receive either 2 × 108 CFU of reconstituted, lyophilized Peru-15 vaccine diluted in CeraVacx buffer or placebo (CeraVacx buffer alone). Approximately 3 months after vaccination, 36 of these volunteers were challenged with approximately 105 CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Among vaccinees, 98% showed at least a fourfold increase in vibriocidal antibody titers. After challenge, 5 (42%) of the 12 placebo recipients and none (0%) of the 24 vaccinees had moderate or severe diarrhea (≥3,000 g of diarrheal stool) (P = 0.002; protective efficacy, 100%; lower one-sided 95% confidence limit, 75%). A total of 7 (58%) of the 12 placebo recipients and 1 (4%) of the 24 vaccinees had any diarrhea (P < 0.001; protective efficacy, 93%; lower one-sided 95% confidence limit, 62%). The total number of diarrheal stools, weight of diarrheal stools, incidence of fever, and peak stool V. cholerae excretion among vaccinees were all significantly lower than in placebo recipients. Peru-15 is a well-tolerated and immunogenic oral cholera vaccine that affords protective efficacy against life-threatening cholera diarrhea in a human volunteer challenge model. This vaccine may therefore be a safe and effective tool to prevent cholera in travelers and is a strong candidate for further evaluation to prevent cholera in an area where cholera is endemic.

scholarly journals TcpF Is a Soluble Colonization Factor and Protective Antigen Secreted by El Tor and Classical O1 and O139 Vibrio cholerae Serogroups

2005 ◽  
Vol 73 (8) ◽  
pp. 4461-4470 ◽  
Author(s):  
Thomas J. Kirn ◽  
Ronald K. Taylor
Keyword(s):  
Vibrio Cholerae ◽  
Protective Antigen ◽  
Secretion System ◽  
Cholera Vaccine ◽  
Infant Mouse ◽  
Bacterial Interactions ◽  
Secretion Pathway ◽  
Extracellular Secretion ◽  
Colonization Factor ◽  
El Tor

ABSTRACT Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was identified in classical isolates of V. cholerae O1 as a soluble factor essential for colonization in the infant mouse cholera model. In the present study, we expanded our analysis of TcpF to include the O1 El Tor and O139 serogroups and investigated how TCP and TcpF act together to mediate colonization. Additionally, we demonstrated that antibodies generated against TcpF are protective against experimental V. cholerae infection in the infant mouse cholera model. This observation, coupled with the fact that TcpF is a potent mediator of colonization, suggests that TcpF should be considered as a component of a polyvalent cholera vaccine formulation.

scholarly journals Expanded Safety and Immunogenicity of a Bivalent, Oral, Attenuated Cholera Vaccine, CVD 103-HgR Plus CVD 111, in United States Military Personnel Stationed in Panama

1999 ◽  
Vol 67 (4) ◽  
pp. 2030-2034 ◽  
Author(s):  
David N. Taylor ◽  
José L. Sanchez ◽  
José M. Castro ◽  
Carlos Lebron ◽  
Carlos M. Parrado ◽  
...  
Keyword(s):  
Low Dose ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
United States Military ◽  
Cholera Vaccine ◽  
Live Attenuated Vaccine ◽  
Oral Cholera Vaccine ◽  
Dose Oral ◽  
El Tor ◽  
Double Chamber

ABSTRACT To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 108 CFU plus CVD 111 at 107 CFU, (b) CVD 103-HgR at 108CFU plus CVD 111 at 106 CFU, (c) CVD 103-HgR alone at 108 CFU, (d) CVD 111 alone at 107 CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.

scholarly journals Preliminary Assessment of the Safety and Immunogenicity of a New CTXΦ-Negative, Hemagglutinin/Protease-Defective El Tor Strain as a Cholera Vaccine Candidate

1999 ◽  
Vol 67 (2) ◽  
pp. 539-545 ◽  
Author(s):  
Jorge A. Benítez ◽  
Luis García ◽  
Anisia Silva ◽  
Hilda García ◽  
Rafael Fando ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Vaccine Candidate ◽  
Immunoglobulin A ◽  
Controlled Study ◽  
Cholera Vaccine ◽  
Double Blind ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
El Tor ◽  
Adult Volunteers

ABSTRACT Vibrio cholerae 638 (El Tor, Ogawa), a new CTXΦ-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled study, no significant adverse reactions were observed in volunteers ingesting strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who received placebo experienced loose stools. The strain strongly colonized the human small bowel, as evidenced by its isolation from the stools of 37 of 42 volunteers. V. cholerae 638, at doses ranging from 4 × 107 to 2 × 109 vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa immunoglobulin A antibody secreting cell responses.

scholarly journals Construction and Characterization of a Nonproliferative El Tor Cholera Vaccine Candidate Derived from Strain 638

2000 ◽  
Vol 68 (11) ◽  
pp. 6411-6418 ◽  
Author(s):  
Edgar Valle ◽  
Talena Ledón ◽  
Bárbara Cedré ◽  
Javier Campos ◽  
Tania Valmaseda ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Adult Rabbit ◽  
Complete Medium ◽  
Cholera Vaccine ◽  
Wild Type ◽  
Infant Mouse ◽  
El Tor ◽  
Candidate Strain

ABSTRACT In recent clinical assays, our cholera vaccine candidate strain,Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyAgene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celAmarker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate.

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.

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