Oral vaccines under development
Salmonella typhi and S. typhimurium belong to the enterobacteriaceae family and are gram negative bacteria. They are transmitted through faecal contamination of water supplies and are of high health significance, causing various diseases such as typhoid fever. The development of oral vaccines for the prevention of these diseases is being researched through the Mucosal Immunization -Cluster Project. Attenuated strains of the two bacteria, that are strains with less disease producing activity, designated ZH9 and WT05 were developed, corresponding to S. typhi and S. typhimurium respectively. Healthy volunteers were given one of the strains in differing doses and the attenuation and immunogenicity monitored. At the lowest dose of 107 colony forming counts (CFU), no response was noted in the immune system of the volunteers. At repeated doses of 108 and 109 CFU, specific antibodies, were developed against the ZH9 strain. The strain did not produce any adverse side effects and was not detected in the blood or the stools of the volunteers. The WT05 strain was also well tolerated with no diarrhoea, although it was shed in stools for a maximum of 23 days depending of the administered dose. At the highest administered dose of 109 CFUs, specific antibodies were also developed. The immune responses in both cases indicate that there is potential for the development of live vaccines in humans. Under the same project to develop recombinant BCG for oral use, the immune response to a non-recombinant oral preparation was assessed in a group of healthy volunteers, who had already been immunised intra-dermally. The vaccine was well tolerated and elicited a T cell response in the majority of volunteers. The results have the potential to be used further for the development of new oral BCG vaccines.
