Safety and immunogenicity of a proteosome-Shigella flexneri 2a lipopolysaccharide vaccine administered intranasally to healthy adults

L. F. Fries, A. D. Montemarano, C. P. Mallett, D. N. Taylor, T. L. Hale, G. H. Lowell

Research output: Contribution to journalArticle

Abstract

We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. flexneri 2a lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins - proteosomes - in normal, healthy adults. A two-dose series of immunizations was given by intranasal spray, and doses of 0.1, 0.4, 1.0, and 1.5 mg (based on protein) were studied in a dose-escalating design. The vaccine was generally well tolerated. The most common reactions included rhinorrhea and nasal stuffiness, which were clearly dose related (P ≤ 0.05). These reactions were self-limited and generally mild. The vaccine elicited S. flexneri 2a LPS-specific immunoglobulin A (IgA), IgG, and IgM antibody-secreting cells (ASCs) in a dose-responsive manner. At doses of 1.0 or 1.5 mg, highly significant (P <0.001) increases in ASCs of all antibody isotypes occurred and 95% of subjects had an ASC response in at least one antibody isotype. Dose-related serum antibody responses were observed, with geometric mean two- to fivefold rises in specific serum IgA and IgG titers and two- to threefold rises in IgM in the 1.0- and 1.5-mg-dose groups (P <0.0001 for each isotype). Elevated serum antibody levels persisted through day 70. Increases in fecal IgG and IgA and also in urinary IgA specific for S. flexneri 2a LPS were demonstrated. These were most consistent and approached statistical significance (P = 0.02 to 0.12 for various measures) on day 70 after the first dose. The magnitude of immune responses to intranasally administered proteosome-S. flexneri 2a LPS vaccine is similar to those reported for live vaccine candidates associated with protective efficacy in human challenge models, and further evaluation of this product is warranted.

Original languageEnglish (US)
Pages (from-to)4545-4553
Number of pages9
JournalInfection and Immunity
Volume69
Issue number7
DOIs
StatePublished - 2001
Externally publishedYes

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Shigella flexneri
Lipopolysaccharides
Vaccines
Antibody-Producing Cells
Immunoglobulin A
Safety
Immunoglobulin G
Immunoglobulin M
Antibodies
Serum
Nose
Antibody Formation
Immunization
Membrane Proteins
Proteins

ASJC Scopus subject areas

  • Immunology

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Safety and immunogenicity of a proteosome-Shigella flexneri 2a lipopolysaccharide vaccine administered intranasally to healthy adults. / Fries, L. F.; Montemarano, A. D.; Mallett, C. P.; Taylor, D. N.; Hale, T. L.; Lowell, G. H.

In: Infection and Immunity, Vol. 69, No. 7, 2001, p. 4545-4553.

Research output: Contribution to journalArticle

Fries, L. F. ; Montemarano, A. D. ; Mallett, C. P. ; Taylor, D. N. ; Hale, T. L. ; Lowell, G. H. / Safety and immunogenicity of a proteosome-Shigella flexneri 2a lipopolysaccharide vaccine administered intranasally to healthy adults. In: Infection and Immunity. 2001 ; Vol. 69, No. 7. pp. 4545-4553.
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