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

We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S, flexneri 2a lipopolysaccharide (LPS) complexed to meni ngococcal outer membrane proteins-proteosomes-in normal, healthy adults, A two-dose series of immunizations was given by intranasal spray, and doses o f 0.1, 0.4, 1.0, and 1.5 mg (based on protein) were studied in a dose-escal ating design. The vaccine was generally well tolerated, The most common rea ctions included rhinorrhea and nasal stuffiness, which were clearly dose re lated (P less than or equal to 0.05). These reactions were self-limited and generally mild. The vaccine elicited S. flexneri 2a LPS-specific immunoglo bulin A (IgA), IgG, and IgM antibody-secreting cells (ASCs) in a dose-respo nsive manner. At doses of 1.0 or 1.5 mg, highly significant (P < 0.001) inc reases 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 spe cific 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 ant ibody levels persisted through day 70, Increases in fecal Ige and IgA and a lso 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 LP S vaccine is similar to those reported for live vaccine candidates associat ed with protective efficacy in human challenge models, and further evaluati on of this product is warranted.