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Infection and Immunity, July 2001, p. 4545-4553, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4545-4553.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Safety and Immunogenicity of a Proteosome-Shigella flexneri 2a Lipopolysaccharide Vaccine Administered Intranasally to Healthy Adults

Louis F. Fries,1,* Andrew D. Montemarano,2,dagger Corey P. Mallett,1 David N. Taylor,2 Thomas L. Hale,2 and George H. Lowell3

Intellivax, Inc., Baltimore, Maryland 212271; Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 203072; and Intellivax International, Inc., Ville St.-Laurent, Québec, H4S 2A1, Canada3

Received 6 December 2000/Returned for modification 9 February 2001/Accepted 6 April 2001

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.

* Corresponding author. Mailing address: Intellivax, Inc., UMBC Technology Center, 1450 South Rolling Rd., Baltimore, MD 21227. Phone: (410) 455-5610. Fax: (410) 455-5606. E-mail: lfries{at}intellivax.com.

dagger Present address: 92 High St., Medford, MA 02155.

Infection and Immunity, July 2001, p. 4545-4553, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4545-4553.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.