1988;47:117C125. an ETEC strain bearing the homologous fimbriae, whereas animals immunized with combined CVD 1204(pGA1-CS2) and CVD 1204(pGA1-CS3) developed antibodies that agglutinated all three test strains. These observations support the feasibility of a multivalent vaccine against shigellosis and ETEC diarrhea consisting of multiple live vectors expressing relevant ETEC antigens. Two bacterial enteric pathogens that have been identified by the World Health Organization as constituting important targets for the development of vaccines are enterotoxigenic (ETEC) and (35, 38). In developing countries, ETEC is a major cause of diarrheal dehydration in infants (4), whereas is the main agent of bacillary R306465 dysentery in young children (35). Both pathogens contribute in a major way to the mortality burden attributable to enteric pathogens (4, 35). ETEC is also the most frequent etiologic agent associated with traveler’s diarrhea (3, 14, 29, 51), whereas in many studies is often the second most incriminated pathogen (14, 29). Traveler’s diarrhea caused by tends to be clinically more severe and debilitating than that caused by ETEC. Both ETEC and are deemed to be worthy targets for immunoprophylaxis of travelers from industrialized countries who visit developing regions of the world (45). Among the promising candidate vaccines against are parenteral O polysaccharide-carrier protein conjugates (7, 8), intranasally administered R306465 proteosomes consisting of outer membrane protein vesicles of group B to which lipopolysaccharide is definitely noncovalently bound (47, 48), and attenuated strains of used as live oral vaccines (9, 34). Within the four varieties (also referred to as organizations), 39 main serotypes and subtypes are identified (15, 35), and epidemiologic 4E-BP1 and experimental observations indicate that immunity is definitely group-specific and, in many instances, serotype-specific (21, 22). As a result, initial success with prototype vaccines will have to be followed by the development of a final vaccine formulation that incorporates a strategy for conferring broad-spectrum safety against the epidemiologically most important serotypes (35, 53). In recent years, candidate human being vaccines against ETEC have been prepared that are based on stimulating intestinal antibodies against R306465 the colonization element fimbriae by which ETEC attaches to enterocytes and on stimulating antitoxin to neutralize heat-labile enterotoxin (LT) (1, 19, 41, 43, 61, 66, 67). Antigens to activate anticolonization immunity have included inactivated fimbriated ETEC whole bacteria (1, 16, 19, 60), purified ETEC fimbriae given in native form (18, 43) or contained within polylactide-polyglycolide microspheres (67), and live oral vaccines consisting of either fimbriated nontoxigenic ETEC strains (36, 37) or of attenuated or serovars Typhi or Typhimurium live vectors expressing ETEC fimbriae and mutant LT or the LT B subunit (26, 31, 42, 54, 55). ETEC vaccines must also address the substantial antigenic heterogeneity among ETEC strains that cause human being diarrheal disease (24, 39, 42). It is widely agreed that an ETEC vaccine should include colonization element antigen I (CFA/I) and coli surface antigens 1 to 6 (CS1 to CS6) fimbrial antigens (42). The candidate ETEC vaccine that is furthest along in medical trials consists of an oral formulation containing a mixture of inactivated, fimbriated ETEC strains that express CFA/I and CS1-6, coadministered in combination with the cholera toxin B subunit (CT-BS) (60, 61). CT and CT-BS elicit cross-reacting antibodies that can neutralize the LT R306465 variant found in ETEC strains in humans (LTh) R306465 (46, 65); CT-BS, by itself, offers conferred short-term safety (for a number of weeks) against diarrhea caused by LT-producing ETEC (6, 56). We have embarked on a long-term project to develop a multivalent cross vaccine to prevent both dysentery and ETEC diarrhea caused by the epidemiologically most important serotypes and antigenic types (34, 39, 53). The approach consists of executive five attenuated strains (representing five epidemiologically and immunologically essential serotypes), each expressing two independent ETEC fimbrial antigens and an antigen to elicit antibodies against LTh (31, 39, 55). Towards this goal,.
