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- Kantele, A., et al.
(författare)
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Safety and immunogenicity of ETVAX (R), an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa
- 2023
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Ingår i: Journal of Travel Medicine. - 1195-1982.
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Tidskriftsartikel (refereegranskat)abstract
- Background: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX (R), a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.Methods: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX (R) or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.Results: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX (R) recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of =2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX (R) recipients (93%) responded to either LTB or O78.Conclusions: This Phase 2b trial is the largest on ETVAX (R) undertaken amongst travellers to date. ETVAX (R) showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.
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- Pakkanen, S. H., et al.
(författare)
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Specific and Cross-reactive Plasmablast Response in Humans after Primary and Secondary Immunization with Vi Capsular Polysaccharide Typhoid Vaccine
- 2017
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Ingår i: Scandinavian Journal of Immunology. - : WILEY. - 0300-9475 .- 1365-3083. ; 86:4, s. 207-215
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Tidskriftsartikel (refereegranskat)abstract
- Secondary immunization with polysaccharide vaccines may imply a risk of hyporesponsiveness. Despite the wide use of typhoid Vi capsular polysaccharide vaccine, its potential tendency to hyporesponsiveness has been inadequately addressed. While previous studies have explored serum antibody responses, we applied a more sensitive approach, a single-cell assay for circulating plasmablasts, to compare primary and secondary responses. Twelve subjects received primary and booster doses of the Vi vaccine (Typherix (R)) at 30-to 37-month intervals. Plasmablasts specific to the Vi or typhoidal O antigens or cross-reactive with paratyphoid and non-typhoidal Salmonella strains were identified as antibodysecreting cells (ASC) with ELISPOT. Before vaccinations, none had plasmablasts specific to the antigens tested. Twelve of 12 subjects showed a Vi-specific response after primary, but only eight of 12 after booster vaccination. All responded to typhoidal O-9,12 antigen after both immunizations. The geometric mean of plasmablasts specific to the Vi antigen was 59 (95% CI 24-119) and 1 (0-54) IgA + IgG + IgM-ASC/10(6) peripheral blood mononuclear cell (PBMC) after primary and booster immunizations, respectively, and 20 (9-49) and 56 (29-103) to the O-9,12 antigen. We detected 1 (0-28) and 17 (6-36) ASC/10(6) PBMC cross-reactive with Salmonella Paratyphi A; 3 (0-30) and 22 (8-48) with S. Paratyphi B; 3 (0-29) and 18 (7-47) with S. Paratyphi C; 19 (10-34) and 51 (26-94) with Salmonella Enteritidis; and 1 (0-35) and 23 (9-52) with Salmonella Typhimurium, respectively. One-third of the vaccinees, although responding to the O-9,12 antigen, failed to respond to the Vi antigen after booster immunization, suggesting hyporesponsiveness in part of the vaccinees. The findings warrant further investigation.
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- Turunen, K., et al.
(författare)
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Clinical aspects of heat-labile and heat-stable toxin-producing enterotoxigenic Escherichia coli: A prospective study among Finnish travellers
- 2020
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Ingår i: Travel Medicine and Infectious Disease. - : Elsevier BV. - 1477-8939. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing travellers' diarrhoea (TD) among visitors to low- and middle-income countries (LMIC). Scant data are available on rates of travel-acquired ETEC producing heat-labile (LT) and/or heat-stable (ST) toxin or its subtypes, STh (human) and STp (porcine) in various geographic regions, and on clinical pictures associated with each toxin. Methods: Using qPCR, we analysed LT, STh, and STp in stools positive for ETEC in a prospective study among 103 Finnish travellers visiting LMIC. They filled in questionnaires and provided stool samples before and after travel. We scrutinized geographic distribution of LT, STh, and STp ETEC findings, and association between these different ETEC subtypes and moderate/severe TD. Results: Among the 103 stool samples positive for ETEC toxins, the rate for LT was 76%, for STh 26%, and STp 41%. The rate for LT-only was 44%, for 5Th-only 6%, STp-only 16%, LT + STh 10%, LT + STp 15%, STh + STp 3%, and LT + STh + STp 8%. Findings varied by destination; the rates of LT, STh, and STp were 79%, 21%, and 57%, respectively, in Southern Asia (n = 14); 85%, 10%, and 20% in South-eastern Asia (n = 20); 84%, 13%, and 29% in Eastern Africa (n = 31); and 56%, 50%, and 63% in Western Africa (n = 32), respectively. Of travellers positive for LT, STh, and STp, 83%, 100%, and 88%, encountered TD; 35%, 55%, and 41% reported moderate/severe TD. STh was associated with moderate/severe TD. Conclusions: Toxin findings varied by destination; multiple toxins were commonly detected. Moderate/severe TD was reported most frequently by subjects with STh-ETEC.
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