Phase I clinical trials of aroA aroD and aroA aroD htrA attenuated S-typhivaccines; effect of formulation on safety and immunogenicity

PBCC211, an aroA aroD derivative of S. typhi strain CDC10 80, was tested in phase I trials as a single dose typhoid fever vaccine. Three different vac cine preparations, reconstituted lyophilized bacteria. freshly grown bacter ia or lyophilized bacteria reconstituted from sachets, were orally administ ered to a total of 86 adult volunteers. An aroA aroD Arl A strain, PBCC222, was also tested in 38 volunteers. Formulation impacted on the determinatio n of a safe and immunogenic dose; reconstituted lyophilized cultures requir ed higher doses than the broth cultures to stimulate seroconversion. Ln gen eral, doses which seroconverted the majority of group members produced unde sirable symptoms regardless of attenuation or formulation. The inability to separate the presence of symptoms from achieving significant immunogenicit y in these aroA aroD or aroA aroD htrA strains precludes their use as singl e dose typhoid vaccines in the formulations tested. Multiple doses of these strains at a lower, safe level may be effective as vectors for foreign ant igens, (C) 2000 Elsevier Science Ltd. All rights reserved.