Safety and Immunogenicity of InvestigationalShigellaConjugate Vaccines in Israeli Volunteers

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of ShigellasonneiandShigellaflexneritype2acovalentlyboundtoPseudomonasaeruginosarecombinantexoprotein A(rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% ofS. sonnei-rEPA recipients and 73 to 77% ofS.flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years,theseremainedhigherthanatprevaccination(P<0.01).TherewasafourfoldorgreaterincreaseinIgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG wasthehighestandmostsustainedclassofLPSantibodies.Reinjectionatday42didnotboostantibodylevels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination withS. sonnei-rEPA andS.flexneri2a-rEPA, respectively. On the basis of these data, further evaluation of theShigellaconjugates for protective efficacy in field trials in Israel was started.