Year: 2014
Type: dissertation
Abstract: Diseases caused by Salmonella (S.) comprise a serious health problem worldwide. Salmonella can cause enteric fever (typhoid fever and paratyphoid fever, caused by S. Typhi and S. Paratyphi A/B/C, respectively) or diarrhea (caused by non-typhoidal Salmonella, NTS serotypes). NTS serotypes can also cause severe invasive salmonellosis (iNTS). Typhoid fever is the only one of these diseases against which there are vaccines in clinical use: the oral live attenuated whole-cell vaccine Salmonella Typhi Ty21a (Ty21a vaccine) and the parenteral Vi capsular polysaccharide vaccine (Vi vaccine). Vaccines against paratyphoid fever and non-typhoid salmonellosis are urgently needed. Until a proper vaccine targeted against these diseases is in clinical use, a lower degree of the cross-protective capacity in currently available vaccines warrants evaluation. This thesis examined the local and systemic antibody responses in volunteers immunized with typhoid vaccines. In addition to measuring S. Typhi-specific responses, this work addressed whether typhoid vaccines have capacity to elicit a cross-reactive immune response against other clinically relevant Salmonellae (paratyphoid or non-typhoid Salmonellae). Comparisons between the immune responses to the two vaccines, Ty21a and Vi, revealed an equal magnitude of typhoid-specific plasmablasts, while the localization of the responses was different: Ty21a elicited a gut-directed plasmablast response while the response to the Vi vaccine appeared more systemic. The Ty21a was found to induce a plasmablast response cross-reactive with S. Paratyphi A and B and with numerous clinically significant NTS serotypes (including the two most common ones, S. Enteritidis and S. Typhimurium). Surprisingly, the Vi vaccine was found to elicit an immune response cross-reactive with S. Paratyphi and the certain NTS. This response was significantly weaker than with the Ty21a vaccine. The central finding of this study was that the Ty21a vaccine elicits a significant intestinal antibody response cross-reactive with S. Paratyphi and most clinically relevant non-typhoid Salmonellae. This finding is especially important in the present situation when vaccines against these pathogens are not available, the mortality rate for iNTS disease in Africa is high, and strains resistant to numerous antimicrobials are emerging around the world. Immunological evidence suggests that the currently available Ty21a vaccine could be used as a surrogate vaccine providing some cross-protection against paratyphoid A and B fever and numerous clinically important NTS serotypes.
Source: Työväentutkimus Vuosikirja
Author: Sari H. Pakkanen
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1899338354