Live oral typhoid vaccine Salmonella Typhi Ty21a - a surrogate vaccine against non-typhoid salmonella?
BACKGROUND
Non-typhoid Salmonella (NTS) is a leading cause of food-borne illness with more than 90 million annual cases and an emerging antimicrobial resistance among the strains worldwide. Paradoxically, no vaccines are available against these pathogens. Numerous NTS strains share surface O-antigens with Salmonella enterica serotype Typhi. As intestinal antibodies against O-antigens have proven protective against NTS in animal experiments, it appears conceivable that the oral whole-cell typhoid vaccine, Salmonella Typhi Ty21a (Vivotif(®)), which effectively elicits intestinal antibodies against O-antigens, could exhibit cross-protective efficacy against NTS. We sought immunological evidence in support of cross-protective efficacy of Ty21a against NTS.


METHODS
35 volunteers receiving Ty21a vaccine and five patients with enteric fever were investigated with ELISPOT for circulating plasmablasts secreting antibodies reactive with Salmonella Typhi and six different NTS serotypes. These plasmablasts were also analysed for homing receptor expressions.


RESULTS
In all vaccinees and patients, a strong gut-directed cross-reactive plasmablast response was found against serotypes sharing the two O-antigens with Salmonella Typhi (O-9,12) (in vaccinees, mean: 95%CI 268: 228-508 and 363: 234-493 plasmablasts/10(6)PBMC against Salmonella Typhi and Enteritidis). Responses against strains sharing one O-antigen (O-12) were weaker (222: 105-338 against Salmonella Typhimurium), while no significant reactivity was detected against strains without typhoidal O-antigens.


CONCLUSIONS
Intestinal antibodies against O-antigens protect against NTS in animal experiments. Ty21a was found to elicit intestinal immune responses cross-reactive with NTS strains sharing O-antigens with Ty21a. These include the most common NTS, Salmonella Enteritidis and Typhimurium. The data suggest that Ty21a may have cross-protective efficacy against numerous NTS strains.
Department of Medicine, Division of Infectious Diseases, 00029 Helsinki University Hospital, Helsinki, Finland. anu.kantele@hus.fi
Anu
A
Kantele
Sari H
SH
Pakkanen
Anja
A
Siitonen
Riitta
R
Karttunen
Jussi M
JM
Kantele
D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D056738:Cross Protection; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006805:Human Experimentation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D012480:Salmonella Infections / Q000517:prevention & control*; D012477:Salmonella enteritidis / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
D000907:Antibodies, Bacterial; D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated