title: Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults.
abstract: Live attenuated Shigella sonnei vaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 10(4) CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulent S. sonnei strain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 10(4) CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.).
authors.affiliation: Department of Clinical Tropical Medicine and Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand punnee.pit@mahidol.ac.th.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Dilara
authors.initials: D
authors.lastname: Islam
authors.affiliation: Department of Clinical Tropical Medicine and Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Supat
authors.initials: S
authors.lastname: Chamnanchanunt
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Nattaya
authors.initials: N
authors.lastname: Ruamsap
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Patchariya
authors.initials: P
authors.lastname: Khantapura
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Department of Clinical Tropical Medicine and Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Chatporn
authors.initials: C
authors.lastname: Kittitrakul
authors.affiliation: Department of Clinical Tropical Medicine and Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Viravarn
authors.initials: V
authors.lastname: Luvira
authors.affiliation: Department of Clinical Tropical Medicine and Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jittima
authors.initials: J
authors.lastname: Dhitavat
authors.affiliation: Department of Enteric Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Malabi M
authors.initials: MM
authors.lastname: Venkatesan
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mason
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Ladaporn
authors.initials: L
authors.lastname: Bodhidatta
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D004405:Dysentery, Bacillary / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012764:Shigella sonnei / Q000276:immunology*; D013785:Thailand; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014838:Volunteers; D055815:Young Adult
chemical_list: D010919:Placebos; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated