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Results for “Shigella Vaccines”

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At least 19 recordsLinked to original sources
PubMed2003

Immune responses elicited against multiple enterotoxigenic Escherichia coli fimbriae and mutant LT expressed in attenuated Shigella vaccine strains.

Shigella and enterotoxigenic Escherichia coli (ETEC) continue to be important causes of diarrheal disease in infants and young children in developing countries and are major etiologic agents of traveler's diarrhea. Since attenuated strains of Shigella have been developed as live oral vaccines against shigellosis, we have adapted these attenuated Shigella strains to serve as carriers of ETEC antigens, thereby constituting a hybrid vaccine. Since protective immunity against ETEC is largely directed against fimbrial antigens (of which there are multiple antigenic types), we have individually expressed four different ETEC fimbriae, including CFA/I, CS2, CS3, and CS4, using deltaguaBA attenuated Shigella vaccine strain CVD 1204 as a prototype live vector. Following mucosal (intranasal) immunization of guinea pigs, serum IgG and mucosal IgA responses were elicited against each fimbrial type. An additional strain was constructed expressing a detoxified version of the human ETEC variant of heat labile toxin (LThK63). Following mucosal immunization of guinea pigs with a mixed inoculum containing five Shigella strains each expressing a different ETEC antigen, immune responses were observed against each ETEC antigen plus the Shigella vector.

Animals↗
PubMed1999

Killed oral Shigella vaccine made from Shigella flexneri 2a protects against challenge in the rabbit model of shigellosis.

The protective efficacy of an orally administered heat-killed virulent strain of Shigella flexneri 2a (5 weekly oral doses) was evaluated in 25 rabbits (14 immunized and 11 non-immunized controls) against challenge with the same strain of Shigella using the rabbit model of shigellosis. All 11 non-immunized rabbits developed bloody diarrhoea following challenge and 6 (54%) died. None of the 14 immunized rabbits developed diarrhoea (all had pellet stools) but 3 (21%) died from causes not associated with diarrhoea. Protection from diarrhoea and dysentery following oral immunization with a killed Shigella species was 100% and highly significant. Death following challenge was 2.5-fold higher in the non-immunized group (p = 0.115) but was not significant. These promising results suggest that further studies should be undertaken to develop a killed oral vaccine against shigellosis.

Administration, Oral↗
PubMed1990

Studies in volunteers to evaluate candidate Shigella vaccines: further experience with a bivalent Salmonella typhi-Shigella sonnei vaccine and protection conferred by previous Shigella sonnei disease.

A bivalent vaccine consisting of Salmonella typhi strain Ty21a containing the 120 MDa plasmid of Shigella sonnei and expressing both S. typhi and S. sonnei lipopolysaccharides (LPS) on its surface was previously shown to protect significantly against S. sonnei disease in experimental challenge studies. However, protective efficacy could not be reconfirmed in volunteers with five subsequent lots of vaccine. One vaccine lot which resembled the initial protective lots of vaccine in biochemical and serological tests, and by electron microscopy, was administered to 16 volunteers who ingested three doses of 10(9) organisms each. Antibody secreting cells (ASC) specific for S. sonnei LPS were detected in the blood of 100% of vaccines, but no protection of these vaccines was demonstrated during a S. sonnei challenge study. To assess the ability of the volunteer model to detect infection-derived immunity, six volunteers who had had clinical shigellosis due to S. sonnei two months earlier were rechallenged with wild-type S. sonnei, together with 12 controls. Prior infection provided 100% protection against febrile illness (p = 0.05) and diarrhea (p = 0.04), thereby validating the volunteer model for assessing Shigella vaccines.

Administration, Oral↗
PubMed2006

Live-attenuated Shigella vaccines.

Several live-attenuated Shigella vaccines, with well-defined mutations in specific genes, have shown great promise in eliciting significant immune responses when given orally to volunteers. These responses have been measured by evaluating antibody-secreting cells, serum antibody levels and fecal immunoglobulin A to bacterial lipopolysaccharide and to individual bacterial invasion plasmid antigens. In this review, data collected from volunteer trials with live Shigella vaccines from three different research groups are described. The attenuating features of the bacterial strains, as well as the immune response following the use of different dosing regimens, are also described. The responses obtained with each vaccine strain are compared with data obtained from challenge trials using wild-type Shigella strains. Although the exact correlates of protection have not been found, some consensus may be derived as to what may constitute a protective immune response. Future directions in the field of live Shigella vaccines are also discussed.

Adolescent↗
PubMed2006

Developing live Shigella vaccines using lambda Red recombineering.

Live attenuated Shigella vaccines have shown promise in inducing protective immune responses in human clinical trials and as carriers of heterologous antigens from other mucosal pathogens. In the past, construction of Shigella vaccine strains relied on classical allelic exchange systems to genetically engineer the bacterial genome. These systems require extensive in vitro engineering of long homologous sequences to create recombinant replication-defective plasmids or phage. Alternatively, the lambda red recombination system from bacteriophage facilitates recombination with as little as 40 bp of homologous DNA. The process, referred to as recombineering, typically uses an inducible lambda red operon on a temperature-sensitive plasmid and optimal transformation conditions to integrate linear antibiotic resistance cassettes flanked by homologous sequences into a bacterial genome. Recent advances in recombineering have enabled modification of genomic DNA from bacterial pathogens including Salmonella, Yersinia, enteropathogenic Escherichia coli, or enterohemorrhagic E. coli and Shigella. These advances in recombineering have been used to systematically delete virulence-associated genes from Shigella, creating a number of isogenic strains from multiple Shigella serotypes. These strains have been characterized for attenuation using both in vivo and in vitro assays. Based on this data, prototypic Shigella vaccine strains containing multiple deletions in virulence-associated genes have been generated.

Bacteriophage lambda↗
PubMed1987

A prospective epidemiologic study of shigellosis in the Israel Defense Forces: implications for the use of shigella vaccines.

Recent development of new shigella vaccines has renewed interest in the current epidemiology of shigellosis in endemic regions. A prospective epidemiologic study of 5,774 soldiers was carried out in the Israel Defense Forces, between the months of May and September 1984. Shigellosis was found to be responsible for half the diarrhea epidemics and only rarely presented as sporadic cases of diarrhea. The epidemics occurred after exposure to field conditions, whereas under fixed military base conditions the finding of a case of shigellosis generally was not associated with an epidemic spread of the disease. It was concluded that, in this population, effective shigella vaccines may provide an important means of preventing epidemics of shigellosis in military units operating outside of permanent bases.

Adolescent↗
PubMed1977

Studies with a new generation of oral attenuated shigella vaccine: Escherichia coli bearing surface antigens of Shigella flexneri.

In an attempt to develop a safe, proliferating, oral, attenuated vaccine against shigellosis, genes that control the synthesis of group- and type-specific somatic antigens of Shigella flexneri 2a were transferred via conjugation to a recipient strain of Escherichia coli. The resultant hybrid (E. coli expressing shigella surface antigens) vaccine strain, PGAI 42-1-15, believed to have a complete (smooth) lipopolysaccharide, was given to volunteers in two vaccination-challenge studies. The vaccine was well tolerated and gave evidence of intestinal proliferation. In trial no. 1, volunteers given two doses of vaccine one month apart were challenged after eight weeks with 10(4) virulent S. flexneri 2a. Attack rates were comparable in vaccinees (50%) and controls (40%). In trial no. 2, vaccinees were given three weekly doses of vaccine and were challenged four weeks later with a small inoculum (10(2)) of S. flexneri 2a. Again, attack rates among vaccinees (47%) and controls (39%) were similar. It is unclear why this theoretically ideal, live shigella vaccine failed to protect against S. flexneri 2a.

Administration, Oral↗
PubMed2003

[The observation of the lymphocyte phenotype change in different lymphoid tissues of mice after intranasal immunization with bivalent Shigella vaccines].

AIM: To observe the changes of lymphocyte phenotype in different lymphoid tissues of mice at various time after intranasal immunization with bivalent Shigella vaccines. METHODS: BALB/c mice were randomly divided into three groups, 30 mice per group. Mice were intranasally immunized respectively with PBS, FSM-2117 or FS-5416 four times (bacterial number was sequentially 5x10(6), 1x10(7),4x10(7)and 4x10(7)CFU/mouse) with two week intervals. Lymphocytes in nasal associated lymphoid tissue (NALT), nasal passage(NP), spleen or Peyer's patch (PP) were isolated on the 7th,30th and 90th day after the last immunization. The phenotype of the lymphocytes was detected by FACS. RESULTS: CD3(+) T cells in NALT, NP and PP increased significantly on the 7th day after the immunization, in which most were CD4(+)T cells. B220(+) cells and CD3(+) T cells increased notably in spleens of FSM-2117 group and FS-5416 group, respectively. The same phenotypic changes still maintained in the NALT, NP and spleen on the 30th day after immunization, but only present in NALT and NP on the 90th day. CONCLUSION: Intranasal inoculation with the two bivalent Shigella vaccines can effectively induce immune responses in different mucosal sites and systematically which can durate for a long time and start to weaken from the tissues distal from nose to those proximal.

Administration, Intranasal↗
PubMedDate not supplied

An update on Shigella vaccines.

Recent advances in the understanding of the molecular virulence mechanisms of Shigella have helped to develop a new generation of candidate Shigella vaccines. Approaches that are currently under active study include construction of hybrid Shigella-E. coli strains, performance of attenuating mutations in vitro on natural Shigella strains and acellular, lipopolysaccharide-based vaccines.

Animals↗
PubMed1993

Strategies for development of potential candidate Shigella vaccines.

Bacillary dysentery, caused by Shigella bacteria, is a major enteric disease responsible for over 200 million infections annually with 650,000 fatal cases. Due to its high communicability, improvement of hygienic standards alone should reduce the spread of dysentery. However, such measures are expensive, and in the communities (e.g. penitentiaries and asylums) or in the areas of the world where bacillary dysentery is most frequently encountered (e.g. in the developing countries) they are not likely to take effect in the reasonably near future. Therefore the possibility of other preventive means such as anti-dysentery vaccines have been explored over the past 40 years. Recently, increased understanding of the molecular biology of bacillary dysentery and the possibility of designing well characterized vaccine strains have increased interest in the field. Several promising vaccine candidates are at various levels of investigations, but to date no Shigella vaccines are available for public health purposes. In this review, beyond the relevant basic information about the pathology, pathomechanism and molecular biology of bacillary dysentery, the various approaches and strategies to construct a safe and immunogenic anti-dysentery vaccine are critically discussed.

Animals↗
PubMed1993

Evaluation of Shigella vaccine safety and efficacy in an intranasally challenged mouse model.

Five Shigella vaccine candidates (EcSf2a-1, EcSf2a-2, Sfl124, T32-Istrati and SMD) were tested for safety and efficacy in Balb/cJ mice using an intranasal challenge model. Experiments in this model suggest that (i) the relative attenuation of vaccines can be determined in mice by intranasal inoculation, (ii) all vaccines tested elicited antibacterial mucosal immunity protecting against pulmonary infection with Shigella flexneri 2a, (iii) protection was associated with serum IgA and/or IgG antibody recognizing the 2a somatic antigen.

Administration, Intranasal↗
PubMed2000

DeltaguaBA attenuated Shigella flexneri 2a strain CVD 1204 as a Shigella vaccine and as a live mucosal delivery system for fragment C of tetanus toxin.

The DeltaguaBA Shigella flexneri 2a vaccine candidate, CVD 1204, was evaluated as a delivery system for the non-toxic C-terminal of tetanus toxin (fragment C), either as a polypeptide expressed in the bacteria or as a DNA vaccine. CVD 1204 was transformed with plasmid pTETnir15 which encodes the fragment C gene (tetC) under the control of the inducible prokaryotic nir15 promoter or a DNA vaccine plasmid pcDNA3tetC which encodes tetC under the eukaryotic hCMV promoter. Guinea pigs immunised intranasally (i.n.) with either recombinant strain mounted a secretory immune response against S. flexneri 2a Lipopolysaccharide (LPS) and were protected against ocular challenge with wild-type S. flexneri 2a. Both strains were effective in eliciting a serum IgG response against fragment C in guinea pigs following i.n. immunisation. Furthermore, serum from guinea pigs immunised with CVD 1204(pTETnir15) contained tetanus toxin neutralising antibodies. These results demonstrate that this S. flexneri 2a vaccine candidate can serve as a vehicle for the delivery of foreign antigens to the systemic immune system while retaining its capacity to serve as a mucosal Shigella vaccine.

Administration, Intranasal↗