SYNTHESIS, CHARACTERIZATION, AND CLINICAL-EVALUATION OF CONJUGATE VACCINES COMPOSED OF THE O-SPECIFIC POLYSACCHARIDES OF SHIGELLA-DYSENTERIAE TYPE-1, SHIGELLA-FLEXNERI TYPE-2A, AND SHIGELLA-SONNEI (PLESIOMONAS-SHIGELLOIDES) BOUND TO BACTERIAL TOXOIDS

The theoretic basis for developing conjugate vaccines, to induce immun oglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the preventi on of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R . Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific pol ysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, th e O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injec ted into young outbred mice subcutaneously as saline solutions contain ing 2.5 mug of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 mug of these conjugates into adult volunteers elicite d mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and a dsorption of the conjugates onto alum did not enhance their immunogeni city. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization anti bodies of the three immunoglobulin classes were similar to or higher t han those of recruits in the Israel Defense Force following shigellosi s caused by S. flexneri type 2a or S. sonnei. These data provide the b asis for evaluating these conjugates to prevent shigellosis.