Salmonella is a pathogenic bacterium. In order to be used as a live vaccine vector, it should be attenuated by various mutations [35,36]. Furthermore, multiple mutations are introduced to reduce the chance of reverting to display virulence. Salmonella is one of the most widely studied live vectors to deliver protective antigens. Recombinant attenuated Salmonella vaccines (RASVs) can attach to, invade and colonize in deep effector lymphoid tissues after mucosal delivery and therefore remodel the host cells that they target as well as promote immunomodulatory effects to induce immune responses in locations where bacteria persist as well as at systemic sites [37,38,39]. Currently, a phase I clinical trial showed that the three S. typhi vaccine vectors—χ9633, χ9639 and χ9640—delivering pneumococcal antigen PspA were safe and well-tolerated [40]. These achievements were made during the process with a final goal of developing a safe RASV suitable for use in newborns/neonates and infants that induces protective immunity to the diversity of S. pneumoniae strains.