Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers

Kärnell, Anders; Liu, An; Zhao, C.-R.; Karlsson, K.; Minh, Nguyen Binh; Lindberg, Alf A.

doi:10.1016/0264-410x(95)80017-8

Cited by 54 publications

(39 citation statements)

References 33 publications

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“…So, it was not possible to attribute the clinical behaviour of the vaccine strain to the introduced mutation. By contrast, when an aroD deletion was introduced into the wellcharacterized wild-type S. flexneri 2a strain 2457T, resulting in vaccine strain SFL1070, it was clearly demonstrated that this mutation afforded measurable attenuation 85 . Similarly, S. dysenteriae 1 strain SC595 caused only low rates of mild diarrhoeal illness when administered to North American volunteers (except in one subject who developed dysentery) 60 .…”

Section: The Importance Of the Parent Strainmentioning

confidence: 96%

“…These mutations include aroD and aroA (which encode enzymes in the aromatic amino-acid biosynthesis pathway; mutation makes mutants auxotrophic for substrates not found in sufficient concentration in mammalian tissues) 85,86 , virG 28, 87 , iuc (which encodes aerobactin) 28 , guaBA (which encodes enzymes involved in guanine-nucleotide biosynthesis) 87,88 , set (which encodes ShET1) and sen (which encodes ShET2) 87,88 .…”

Section: Selection Of Attenuating Mutationsmentioning

confidence: 99%

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

et al. 2007

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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...

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Section: The Importance Of the Parent Strainmentioning

confidence: 96%

Section: Selection Of Attenuating Mutationsmentioning

confidence: 99%

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

et al. 2007

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“…In humans, systemic and mucosal Abs are directed primarily to Shigella LPS, with a lesser response against the invasion plasmid Ags (Ipa) 3 A, B, C, and D (2). Some field studies and phase 1 vaccine trials have shown a correlation between protection and Abs against LPS (3,4), whereas other trials have not (5,6). For example, in an epidemiological study in Peru, investigators found that in contrast to anti-LPS Ab, anti-Ipa Ab may limit the spread and severity of infection (7).…”

mentioning

confidence: 99%

Production of IFN-γ and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain

Samandari

Kotloff

Losonsky

et al. 2000

The Journal of Immunology

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Volunteers were orally administered invasive, non-Shiga toxin-producing Shigella dysenteriae 1 to establish a challenge model to assess vaccine efficacy. In stepwise fashion, four separate groups were given 3 × 102, 7 × 103, 5 × 104, or 7 × 105 CFU. Using PBMC, proliferative responses and cytokine production were measured to S. dysenteriae whole-cell preparations and to purified recombinant invasion plasmid Ags (Ipa) C and IpaD. Anti-LPS and anti-Ipa Abs and Ab-secreting cells were also evaluated. Preinoculation PBMC produced considerable quantities of IL-10 and IFN-γ, probably secreted by monocytes and NK cells, respectively, of the innate immune system. Following inoculation, PBMC from 95 and 87% of volunteers exhibited an increased production of IFN-γ and IL-10, respectively, in response to Shigella Ags. These increases included responses to IpaC and IpaD among those volunteers receiving the lowest inoculum. No IL-4 or IL-5 responses were detected. Whereas there were no Ab or Ab-secreting cell responses in volunteers receiving the lowest inoculum, other dose groups had moderate to strong anti-LPS and anti-Ipa responses. These results suggest that in humans, type 1 responses play an important role in mucosal and systemic immunity to S. dysentariae 1.

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“…In support of this notion, there is an emerging consensus that mucosal immunity to HIV-1 provides an important barrier against sexually acquired HIV-1 (6,19). Moreover, attenuated oral Shigella strains retain the ability to enter colonic mucosal lymphoid tissues and induce both mucosal and systemic immune responses (13,14,16). Unfortunately, due to the restricted host specificity of Shigella, we could not directly assess the capacity of our prototype Shigella HIV-1 DNA vaccine vector to induce mucosal responses following oral administration.…”

Section: Discussionmentioning

confidence: 98%

Vaccination with aShigellaDNA Vaccine Vector Induces Antigen-Specific CD8⁺T Cells and Antiviral Protective Immunity

Shata

Hone

2001

J Virol

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A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env (vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8؉ -T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8 ؉ T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since the Shigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8 ؉ T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.

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Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers

Cited by 54 publications

References 33 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

Production of IFN-γ and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain

Vaccination with aShigellaDNA Vaccine Vector Induces Antigen-Specific CD8⁺T Cells and Antiviral Protective Immunity

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Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers

Cited by 54 publications

References 33 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

Production of IFN-γ and IL-10 to Shigella Invasins by Mononuclear Cells from Volunteers Orally Inoculated with a Shiga Toxin-Deleted Shigella dysenteriae Type 1 Strain

Vaccination with aShigellaDNA Vaccine Vector Induces Antigen-Specific CD8+T Cells and Antiviral Protective Immunity

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Product

Resources

About

Vaccination with aShigellaDNA Vaccine Vector Induces Antigen-Specific CD8⁺T Cells and Antiviral Protective Immunity