Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

O’Ryan, Miguel; Vidal, Roberto; Canto, Felipe Del; Salazar, Juan Carlos; Montero, David A.

doi:10.1080/21645515.2015.1011578

Cited by 46 publications

(28 citation statements)

References 194 publications

(185 reference statements)

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“…The most common CU-CFs worldwide belong to the α (CFA/I, CS1, CS2, CS4, CS5, CS14, CS17, and CS19) and γ 3 families (CS3 and CS6); these are the same CU-CFs that have been included in vaccine candidate formulations (O'Ryan et al, 2015; Zhang and Sack, 2015). CFs of the CU-families γ 2 and κ are not the most common in ETEC strains (Isidean et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies, including characterization of ETEC isolates worldwide, have been the basis for selection of the most widespread antigens for vaccine development. Both enterotoxins and ETEC adhesins have been proposed and tested as components for vaccine candidates (Isidean et al, 2011; O'Ryan et al, 2015; Zhang and Sack, 2015). Thus, CFs CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, and CS7, or their components, have been included in several formulations, however none of these candidates have passed phase III trials (O'Ryan et al, 2015; Zhang and Sack, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli

Canto

O’Ryan

Pardo

et al. 2017

Front. Cell. Infect. Microbiol.

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Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea worldwide. Among the 25 different ETEC adhesins, 22 are known as “colonization factors” (CFs), of which 17 are assembled by the chaperone-usher (CU) mechanism. Currently, there is no preventive therapy against ETEC, and CFs have been proposed as components for vaccine development. However, studies of diarrhea-causing ETEC strains worldwide indicate that between 15 and 50% of these are negative for known CFs, hindering the selection of the most widespread structures and suggesting that unknown adhesins remain to be identified. Here, we report the result of a comprehensive analysis of 35 draft genomes of ETEC strains which do not carry known adhesin genes; our goal was to find new CU pili loci. The phylogenetic profiles and serogroups of these strains were highly diverse, a majority of which produced only the heat-labile toxin. We identified 10 pili loci belonging to CU families β (1 locus), γ2 (7 loci), κ (1 locus), and π (1 locus), all of which contained the required number of open reading frames (ORFs) to encode functional structures. Three loci were variants of previously-known clusters, three had been only-partially described, and four are novel loci. Intra-loci genetic variability identified would allow the synthesis of up to 14 different structures. Clusters of putative γ2-CU pili were most common (23 strains), followed by putative β-CU pili (12 strains), which have not yet been fully characterized. Overall, our findings significantly increase the number of ETEC adhesion genes associated with human infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli

Canto

O’Ryan

Pardo

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Vaccine development remains a high priority given the disease burden (4, 5), increasing antibiotic resistance (6), and an increasing appreciation of the postinfectious sequelae associated with shigellosis (7, 8). Shigella flexneri accounts for 30 to 60% of shigellosis cases in developing regions, necessitating coverage of prevalent S.…”

Section: Introductionmentioning

confidence: 99%

“…Several vaccine approaches are under active investigation, including live-attenuated vaccines, inactivated whole-cell vaccines, subcellular vaccines, and purified subunit vaccines, such as the O-SP conjugate vaccines (8, 12). The lack of a clear correlate of protection, insufficient relevant disease animal models, and challenges with the induction of adequate mucosal immune responses among the youngest age groups in the developing world have hampered Shigella vaccine development over the past several decades (16–18).…”

Section: Introductionmentioning

confidence: 99%

Safety and Immunogenicity of a Candidate Bioconjugate Vaccine against Shigella flexneri 2a Administered to Healthy Adults: a Single-Blind, Randomized Phase I Study

Riddle

Kaminski

Paolo

et al. 2016

Clin Vaccine Immunol

126

107

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Several candidate vaccines against Shigella spp. are in development, but the lack of a clear correlate of protection from challenge with the induction of adequate immune responses among the youngest age groups in the developing world has hampered Shigella vaccine development over the past several decades. Bioconjugation technology, exploited here for an Shigella flexneri 2a candidate vaccine, offers a novel and potentially cost-effective way to develop and produce vaccines against a major pathogen of global health importance. Flexyn2a, a novel S. flexneri 2a bioconjugate vaccine made of the polysaccharide component of the S. flexneri 2a O-antigen, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for safety and immunogenicity among healthy adults in a single-blind, phase I study with a staggered randomization approach. Thirty subjects (12 receiving 10 μg Flexyn2a, 12 receiving Flexyn2a with aluminum adjuvant, and 6 receiving placebo) were administered two injections 4 weeks apart and were followed for 168 days. Flexyn2a was well-tolerated, independently of the adjuvant and number of injections. The Flexyn2a vaccine elicited statistically significant S. flexneri 2a lipopolysaccharide (LPS)-specific humoral responses at all time points postimmunization in all groups that received the vaccine. Elicited serum antibodies were functional, as evidenced by bactericidal activity against S. flexneri 2a. The bioconjugate candidate vaccine Flexyn2a has a satisfactory safety profile and elicited a robust humoral response to S. flexneri 2a LPS with or without inclusion of an adjuvant. Moreover, the bioconjugate also induced functional antibodies, showing the technology's features in producing a promising candidate vaccine. (This study has been registered at ClinicalTrials.gov under registration no. NCT02388009.)

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“…Dukoral ® may produce some cross protection against enterotoxigenic Escherichia coli diarrhea. However, additional evidence is required to support the recommendation for its use for this indication [48][49][50] .…”

Section: Vaccines For Food and Water-borne Diseasesmentioning

confidence: 99%

Preventing diseases in round-the-world travelers: a contemporary challenge for travel medicine advice

Rodrigues

Moreira

2018

Rev. Soc. Bras. Med. Trop.

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Providing advice for travelers embarking on long-term trips poses a challenge in travel medicine. A long duration of risk exposure is associated with underuse of protective measures and poor adherence to chemoprophylaxis, increasing the chances of acquiring infections. Recently, in our clinic, we observed an increase in the number of travelers undertaking round-the-world trips. These individuals are typically aged around 32 years and quit their jobs to embark on one-to-two-year journeys. Their destinations include countries in two or more continents, invariably Southeast Asia and Indonesia, and mostly involve land travel and visiting rural areas. Such trips involve flexible plans, increasing the challenge, especially with regard to malaria prophylaxis. Advising round-the-world travelers is time-consuming because of the amount of information that must be provided to the traveler. Advisors must develop strategies to commit the traveler to his/her own health, and verify their learnings on disease-prevention measures. Contacting the advisor after the appointment or during the trip can be helpful to clarify unclear instructions or diagnosis made and prescriptions given abroad. Infectious diseases are among the most frequent problems affecting travelers, many of which are preventable by vaccines, medicines, and precautionary measures. The dissemination of counterfeit medicines, particularly antibiotics and antimalarial medicines, emphasizes the need for travelers to carry medicines that they may possibly need on their trip. Additional advice on altitude, scuba diving, and other possible risks may also be given. Considering the difficulties in advising this group, we present a review of the main recommendations on advising these travelers.

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Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

Cited by 46 publications

References 194 publications

Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli

Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli

Safety and Immunogenicity of a Candidate Bioconjugate Vaccine against Shigella flexneri 2a Administered to Healthy Adults: a Single-Blind, Randomized Phase I Study

Preventing diseases in round-the-world travelers: a contemporary challenge for travel medicine advice

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