Abstract
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 x 10(2), 7 x 10(3), 5 x 10(4), or 7 x 10(5) 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-gamma, 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-gamma 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adhesins, Bacterial*
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Administration, Oral
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Adolescent
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Adult
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Antibodies, Bacterial / biosynthesis
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Antibody-Producing Cells / immunology
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Antibody-Producing Cells / metabolism
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology*
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Bacterial Toxins / administration & dosage
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology*
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Bacterial Vaccines / administration & dosage
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Bacterial Vaccines / genetics
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Bacterial Vaccines / immunology*
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Colony Count, Microbial
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Dose-Response Relationship, Immunologic
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Dysentery, Bacillary / immunology
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Dysentery, Bacillary / metabolism
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Dysentery, Bacillary / prevention & control
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Gene Deletion
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Humans
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Interferon-gamma / biosynthesis*
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Interleukin-10 / biosynthesis*
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Interleukin-12 / biosynthesis
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Interleukin-15 / biosynthesis
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Interleukin-2 / biosynthesis
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Interleukin-4 / biosynthesis
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Interleukin-5 / biosynthesis
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Kinetics
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Leukocytes, Mononuclear / immunology*
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / microbiology
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Lymphocyte Activation
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Shiga Toxins
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Shigella dysenteriae / genetics
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Shigella dysenteriae / immunology*
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Transforming Growth Factor beta / biosynthesis
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology*
Substances
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Adhesins, Bacterial
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Antibodies, Bacterial
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Bacterial Proteins
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Bacterial Toxins
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Bacterial Vaccines
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Interleukin-15
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Interleukin-2
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Interleukin-5
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Shiga Toxins
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Transforming Growth Factor beta
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Vaccines, Synthetic
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invasin, Yersinia
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Interleukin-10
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Interleukin-12
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Interleukin-4
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Interferon-gamma