Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in adult Vietnamese volunteers

An, Li; Kärnell, Anders; Huan, Pham Thi; Cam, Phung Dac; Minh, Nguyen Binh; Tram, L.N.; Quy, Nguyen Phu; Trach, Dang Duc; Karlsson, K.; Lindberg, Gunilla; Lindberg, Alf A.

doi:10.1016/0264-410x(93)90015-p

Cited by 39 publications

(20 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Does this mean that most live oral Shigella vaccines will be poorly immunogenic in developing country populations? The response of Vietnamese adults 83 and children 108 to the ingestion of S. flexneri Y strain SFL124 (an aroD-deletion mutant) and the efficacy of the SmD and T32 live oral Shigella vaccines in subjects in Yugoslavia (late 1960s and early 1970s) 69,70 and China (1980s) 78 , respectively, suggest not. A single 2×10 9 CFU dose of SFL124 was administered to 15 Vietnamese adult volunteers, whereas another 15 subjects ingested three doses (at an interval of two days between doses) 83 .…”

Section: Intestinal Barrier In Developing Country Populationsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

et al. 2007

View full text Add to dashboard Cite

More than 50 years of research has yielded numerous Shigella vaccine candidates that have exemplified both the promise of vaccine-induced prevention of shigellosis and the impediments to developing a safe and effective vaccine for widespread use, a goal that has yet to be attained. This Review discusses the most advanced strategies for Shigella vaccine development, the immune responses that are elicited following disease or vaccination, the factors that have accelerated or impeded Shigella vaccine development and our ideas for the way forward.At the end of the 19th century, as epidemics of bacillary dysentery accompanied by high mortality spread across Japan, the young microbiologist Kiyoshi Shiga examined dysenteric stools and isolated a bacterium that was agglutinated by serum from convalescent patients but not from patients with acute disease [1][2][3] (FIG. 1). That bacterium -known today as Shigella dysenteriae 1 -was the first identified member of the genus Shigella. Four Correspondence to M.L. mlevine@medicine.umaryland.edu. Competing interests statement:The authors declare no competing financial interests. Links NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptShigella species (or groups) are now recognized: S. dysenteriae (group A), which has 15 serotypes; Shigella flexneri (group B), which has 14 classical serotypes and subserotypes; Shigella boydii (group C), which has 20 serotypes; and Shigella sonnei (group D), which has single serotype 4 (TABLE 1).There has been resurgent interest in Shigella as a human pathogen, driven by the availability of more precise data on the disease burden 5-8 , emerging antibiotic resistance 9,10 and the fact that mucosally invasive Shigella, which often cause dysentery (gross blood in diarrhoeal stools), are less amenable to the salutary effects of oral rehydration than non-invasive pathogens that cause watery diarrhoea, such as Vibrio cholerae and enterotoxigenic Escherichia coli. The target populations for the use of Shigella vaccines include infants and young children in developing countries (in which the peak incidence occurs at 12-47 months of age and the S. flexneri serotypes predominate) 5-7 .S. dysenteriae 1, which produces Shiga toxin and typically carries R factors that encode resistance to multiple antibodies, waxes and wanes as a cause of epidemic severe disease in the world's least developed countries [11][12][13][14] Few bacterial pathogens have had their pathogenesis or interactions with mammalian tissues elucidated so precisely at the cellular and subcellular levels as Shigella spp. 20,21 Nevertheless, progress in attaining safe and effective Shigella vaccines has faltered. Herein, we review recent and old clinical trials that have evaluated the safety, immunogenicity and efficacy of candidate Shigella vaccines. We relate the bassis for the most popular strategies (BOX 2), the relevance of the different immune responses measured, the factors that have favoured or impeded vaccine development and, most importantly, the less...

show abstract

Section: Intestinal Barrier In Developing Country Populationsmentioning

confidence: 99%

“…In the case of the S. flexneri Y strain SF1, an aroD mutation was introduced, resulting in attenuated putative vaccine candidate SFL124 (REF. 83). Subsequently, however, when the wild-type S. flexneri Y parent strain SF1 was fed to North American volunteers, it was only minimally pathogenic 84 .…”

Section: The Importance Of the Parent Strainmentioning

confidence: 99%

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

et al. 2007

View full text Add to dashboard Cite

show abstract

“…given to adult Vietnamese volunteers (14,15). Plasmid pNV143, which carries the glucosyl transferase gene (gtr) of phage SfX, was transferred to strain SFL124 by electroporation to study the expression of group-specific antigen 7, 8.…”

mentioning

confidence: 99%

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

Huan

Taylor

Lindberg

et al. 1995

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis.

show abstract

“…They are safe, (18,19), and S. flexneri SFL1070 also seems safe and immunogenic at a dose of 10 8 live bacteria (13). They are thus promising not only as vaccine candidates for immunizing against infections by homologous serotypes but also as delivery systems for protective antigens from other pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…These strains have been proven to be safe, immunogenic, and highly protective when used as live oral vaccines in Macaca fascicularis monkeys (14)(15)(16). Safety and immunogenicity studies with humans have given very promising results (13,18,19).…”

mentioning

confidence: 99%

Expression of Shigella dysenteriae serotype 1 O-antigenic polysaccharide by Shigella flexneri aroD vaccine candidates and different S. flexneri serotypes

et al. 1995

View full text Add to dashboard Cite

show abstract

Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in adult Vietnamese volunteers

Cited by 39 publications

References 12 publications

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

Expression of Shigella dysenteriae serotype 1 O-antigenic polysaccharide by Shigella flexneri aroD vaccine candidates and different S. flexneri serotypes

Contact Info

Product

Resources

About