Vaccine 32 (2014) 544–551 Contents lists available at ScienceDirect Vaccine j our nal homep ag e: www.elsevier.com/locate/vaccine Cross-reactive immune response elicited by parenteral Vi polysaccharide typhoid vaccine against non-typhoid Salmonellae Sari H. Pakkanen a,b , Jussi M. Kantele c , Christian Herzog d , Anu Kantele a,b,e,∗ a Department of Bacteriology and Immunology, Haartman Institute, POB 21, 00014 University of Helsinki, Helsinki, Finland b Department of Medicine, Division of Infectious Diseases, POB 348, 00029 Helsinki University Hospital, Helsinki, Finland c Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland d Swiss Tropical and Public Health Institute, Basel, Switzerland e Institute of Clinical Medicine, Department of Medicine, POB 20, 00014 University of Helsinki, Helsinki, Finland a r t i c l e i n f o Article history: Received 4 July 2013 Received in revised form 13 October 2013 Accepted 2 December 2013 Available online 14 December 2013 Keywords: Salmonella Typhi Ty21a Non-typhoid Salmonella Typherix Vi polysaccharide Antibody-secreting cell Cross-reactive a b s t r a c t Background: Despite 155 000 deaths and over 90 million cases – and the current emergence of antimicro- bial resistance – no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine. Materials and methods: Volunteers immunized with the Vi polysaccharide (Typherix ® ; n = 25) were inves- tigated for circulating plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif ® ), as partly presented in our previous study. The cross-reactive plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions. Results: 49 out of 50 vaccinees showed a cross-reactive plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19–55 and 363: 234–493 plasmablasts/10 6 PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8–38 and 222: 105–338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive plasmablasts elicited by the Vi vaccine had systemic homing properties. Conclusions: The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction There are no vaccines available against non-typhoid Salmonellae (NTS). Recently, it has been shown that the oral Salmonella Typhi Ty21a vaccine elicits a cross-reactive immune response against NTS Abbreviations: ALS, antibodies in lymphocyte supernatants; ASC, antibody- secreting cell; CLA, cutaneous lymphocyte antigen; HR, homing receptor; iNTS, invasive non-typhoid Salmonella; NTS, non-typhoid Salmonella; PBMC, peripheral blood mononuclear cells; PBS, phosphate buffered saline. ∗ Corresponding author at: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, POB 348, FIN-00029 HUS, Finland. Tel.: +358 9 4711; fax: +358 9 471 75900. E-mail addresses: sari.pakkanen@helsinki.fi (S.H. Pakkanen), jussi.kantele@utu.fi (J.M. Kantele), anu.kantele@hus.fi, anu.kantele@hotmail.com (A. Kantele). strains [1] expressing one (O-12) or both (O-9,12) of the typhoidal O-antigens. These NTS strains include the two most common ones, Salmonella enterica subspecies enterica serotype Enteritidis (S. Enteritidis) and S. Typhimurium. We have lately shown that an immune response to typhoidal O-antigens is produced both by the Ty21a vaccine and the Vi capsular polysaccharide typhoid prepa- ration [2], the latter presumably because of the trace amount of LPS remaining even after purification. This opens up the interest- ing possibility of also the Vi vaccine eliciting an immune response cross-reactive with NTS strains sharing O-antigens of S. Typhi. S. enterica subspecies enterica includes typhoidal serotypes (Typhi and Paratyphi) causing enteric fever (typhoid and paraty- phoid), and approximately 2500 NTS serotypes causing mainly gastroenteritis, but also invasive NTS (iNTS) disease [3]. NTS annu- ally accounts for more than 90 million cases of gastroenteritis 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2013.12.001