 The use of attenuated Salmonella strains that are unable to cause clinical disease but trigger a self-limiting infection leading to stimulation of protective immunity presents an attractive alternative to killed and subunit vaccines. Live, attenuated Salmonella strains have been shown to be excellent carriers, or vectors, for prokaryotic or eukaryotic antigens, being able to stimulate strong systemic and local immune responses against the expressed antigens. Three Salmonella Typhi strains have been engineered to express a gene encoding the alpha-helical domain of the Streptococcus pneumoniae surface protein, PspA, and will serve as live biological vaccine vectors in the proposed clinical trial to evaluate maximum safe and tolerable single dose levels after their oral administration to subjects. In this Phase I study, healthy young adults 18-40 years of age will participate in a dose escalating, dose sequential study divided into four Arms to receive doses of 107, 108, 109 and 1010 CFU. Each Arm 1-4 will consist of 3 groups of 5 subjects per group to receive a single oral dose of one of three recombinant attenuated S. Typhi vaccine vectors producing the pneumococcal antigen PspA. Each group per Arm will receive the same dose of one of the three vaccines for a total of 60 subjects 15 subjects per dose-escalating Arm, 3 groups per Arm, 5 subjects per group. Subject participation lasts 6 months after receiving the oral vaccine dosage with approximately the first 12-15 days study Days 0-14 in confinement. Release criteria include 2 negative blood cultures in a row through study Day 7 inpatient monitoring for 8 days and 2 negative stool cultures in a row through study Day 5. The objectives of the study are 1 to evaluate maximum safe tolerable single dose levels of the three recombinant attenuated S. Typhi vaccine vectors using dose-escalation, dose-sequential studies in healthy adult subjects, and 2 to evaluate immunogenicity of the three recombinant attenuated S. Typhi vaccine vectors with regard to their abilities to induce mucosal and systemic antibody responses to the S. pneumoniae PspA and S. Typhi antigens. The vaccines are not anticipated to prevent disease. Although the immune responses generated by the vaccine vectors may confer some degree of protection against future infection with S. pneumoniae and S. Typhi, such protection is incidental. It is not the goal of this study to develop or test either a pneumonia or typhoid vaccine, but to select the S. Typhi vector that provides optimal delivery of the PspA antigen in a safe and immunogenic manner. 