TLP01, an mshA mutant of Vibrio cholerae O139 as vaccine candidate against cholera

Ledón, Talena; Ferrán, Beatriz; Pérez, Celso; Suzarte, Edith; Vichi, J; Marrero, Karen; Oliva, Reynaldo; Fando, Rafael

doi:10.1016/j.micinf.2012.04.004

Cited by 16 publications

(8 citation statements)

References 46 publications

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“…Phage display, since its first description [47] and introduction into laboratory practice [48] , has proven to be useful in selecting antigens derived from phages, either using the phage clone itself or the synthetic mimotopes, for vaccine development against diseases, such as Burkitt's lymphoma [49] , melanoma [50] , colorectal cancer [51] , hepatitis B virus [52] , and rotavirus [53] ; or against pathogens, such as Vibrio cholera [54] , Candida albicans [55] , and Brugia malayi [56] .…”

Section: Discussionmentioning

confidence: 99%

Mimotope-Based Vaccines of Leishmania infantum Antigens and Their Protective Efficacy against Visceral Leishmaniasis

et al. 2014

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BackgroundThe development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera.Methodology/Main FindingsTwenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin), showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies.Conclusions/SignificanceThis study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the parasite burden. This is the first study that describes phage-displayed peptides as successful immunogens in vaccine formulations against VL.

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Section: Discussionmentioning

confidence: 99%

Mimotope-Based Vaccines of Leishmania infantum Antigens and Their Protective Efficacy against Visceral Leishmaniasis

et al. 2014

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“…A recombinant strain with the protective antigen genes that replaced virulence-associated genes was successfully constructed; this candidate strain could potentially be utilized to further evaluate immune response. Further evaluation of the stability of the vaccine is warranted, as well as further investigation regarding its ability to protect against CTXФ infection in vivo (21,22).…”

Section: Discussionmentioning

confidence: 99%

Construction and characterization of a Vibrio cholerae serogroup O139 vaccine candidate by genetic engineering

Cheng

Zhou

Kan

et al. 2014

Molecular Medicine Reports

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The present study aimed to construct and evaluate the live attenuated Vibrio cholerae serogroup O139 vaccine candidate, in which genes encoding protective antigens were integrated into the chromosomal DNA. Using the initial strain, O139-ZJ9693, the toxin-linked cryptic (TLC) and cholera toxin (CTX) genetic elements and repeats in the toxin (RTX) gene cluster were deleted from its chromosomal DNA, and the cholera toxin genes, ctxB and rstR, were transferred into the chromosome to construct the candidate vaccine strain. The expression of ctxB and the vaccine virulence were then examined. Polymerase chain reaction (PCR), enzymatic digestion and electrophoresis were performed to confirm that TLC, CTX and RTX were deleted, and that ctxB and rstR were transferred into the vaccine candidate DNA. According to the preliminary evaluation, the ctxB gene exhibited cholera toxin subunit B expression, and no enterotoxigenic or cytotoxic effects were observed in this strain. In conclusion, a recombinant strain containing genes encoding protective antigens that replaced virulence-associated genes was successfully constructed in the present study; this candidate strain may have the potential to be utilized to further evaluate the immune response.

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“…152 Additionally, it conferred protection against challenge with the wild-type Bengal which encodes the major structural subunit of the mannose-sensitive haemagglutinin (MSH) pilus. 153 The logic behind this mutation is based on the fact that the MSH pilus is A c c e p t e d M a n u s c r i p t 36 the receptor for transduction of the VGJ phage, which can eventually carry and transfer the CTX phage genome into a toxin co-regulated pilus (TCP) negative strain. Therefore, this mutation may prevent reversion to a toxigenic phenotype.…”

Section: Iem 108mentioning

confidence: 99%

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses andVibrio cholerae

O’Ryan

Vidal

Canto

et al. 2015

Human Vaccines & Immunotherapeutics

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Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

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TLP01, an mshA mutant of Vibrio cholerae O139 as vaccine candidate against cholera

Cited by 16 publications

References 46 publications

Mimotope-Based Vaccines of Leishmania infantum Antigens and Their Protective Efficacy against Visceral Leishmaniasis

Mimotope-Based Vaccines of Leishmania infantum Antigens and Their Protective Efficacy against Visceral Leishmaniasis

Construction and characterization of a Vibrio cholerae serogroup O139 vaccine candidate by genetic engineering

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses andVibrio cholerae

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