TY - JOUR
T1 - A phase I trial of WRSS1, a Shigella sonnei live oral vaccine in Bangladeshi adults and children
AU - Raqib, Rubhana
AU - Sarker, Protim
AU - Zaman, K.
AU - Alam, Nur Haque
AU - Wierzba, Thomas F.
AU - Maier, Nicole
AU - Talukder, Kaisar
AU - Baqui, Abdullah Hel
AU - Suvarnapunya, Akamol E.
AU - Qadri, Firdausi
AU - Walker, Richard I.
AU - Fix, Alan
AU - Venkatesan, Malabi M.
N1 - Funding Information:
This research study was funded by PATH, an international non-profit organization that works to improve the health of people around the world by advancing technologies, strengthening systems and encouraging healthy behaviors. PATH participated in the design of the studies, interpretation of results and review of this manuscript. icddr,b acknowledges with gratitude PATH’s commitment to its research efforts. icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. We are greatly indebted to the late Dr. Lillian Van de Verg for her significant contribution towards study design, implementation and support for this study. We acknowledge the study participants for their consent to participate in the study and cordially allowing the scheduled/unscheduled visits of the field staff to their house/home. We appreciate the tedious works of clinical, field, data management and laboratory staff as well as the unblinded randomization team to make the study successful. We thank the project manager, medical monitor, study monitors and data management team of the Contract Research Organization (Emmes Corporation) for their guidance and critical review of the study procedures, source documents and database. We thank Dr. Robert Kaminski at WRAIR for providing S. sonnei LPS. Special thanks to Mr. Ahsanul Haque for his assistance in data analysis for the manuscript.
Funding Information:
This research study was funded by PATH, an international non-profit organization that works to improve the health of people around the world by advancing technologies, strengthening systems and encouraging healthy behaviors. PATH participated in the design of the studies, interpretation of results and review of this manuscript. icddr,b acknowledges with gratitude PATH’s commitment to its research efforts. icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support.
Publisher Copyright:
© 2019, © 2019 Taylor & Francis Group, LLC.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Shigella sonnei live vaccine candidate, WRSS1, which was previously evaluated in US, Israeli and Thai volunteers, was administered orally to Bangladeshi adults and children to assess its safety, clinical tolerability and immunogenicity. In a randomized, placebo-controlled, dose-escalation, age-descending study, 39 adults (18–39 years) and 64 children (5–9 years) were enrolled. Each adult cohort (n = 13) received one dose of 3x104, or three doses of 3 × 105 or 3 × 106 colony forming unit (CFU) of WRSS1 (n = 10) or placebo (n = 3). Each child cohort (n = 16) received one dose of 3x103, or three doses of 3x104, 3x105, or 3 × 106 CFU WRSS1 (n = 12) or placebo (n = 4). WRSS1 elicited mostly mild and transient reactogenicity events in adults and children. In the 3 × 106 dose group, 50% of the adults shed the vaccine; no shedding was seen in children. At the highest dose, 100% of adults and 40% of children responded with a ≥ 4-fold increase of S. sonnei LPS-specific IgA antibody in lymphocyte supernatant (ALS). At the same dose, 63% of adults and 70% of children seroconverted with IgA to LPS, while in placebo, 33% of adults and 18% of children seroconverted. Both the vaccinees and placebos responded with fecal IgA to LPS, indicating persistent exposure to Shigella infections. In conclusion, WRSS1 was found safe up to 106 CFU dose and immunogenic in adults and children in Bangladesh. These data indicate that live, oral Shigella vaccine candidates, including WRSS1 can potentially be evaluated in toddlers and infants (<2 years of age), who comprise the target population in an endemic environment.
AB - Shigella sonnei live vaccine candidate, WRSS1, which was previously evaluated in US, Israeli and Thai volunteers, was administered orally to Bangladeshi adults and children to assess its safety, clinical tolerability and immunogenicity. In a randomized, placebo-controlled, dose-escalation, age-descending study, 39 adults (18–39 years) and 64 children (5–9 years) were enrolled. Each adult cohort (n = 13) received one dose of 3x104, or three doses of 3 × 105 or 3 × 106 colony forming unit (CFU) of WRSS1 (n = 10) or placebo (n = 3). Each child cohort (n = 16) received one dose of 3x103, or three doses of 3x104, 3x105, or 3 × 106 CFU WRSS1 (n = 12) or placebo (n = 4). WRSS1 elicited mostly mild and transient reactogenicity events in adults and children. In the 3 × 106 dose group, 50% of the adults shed the vaccine; no shedding was seen in children. At the highest dose, 100% of adults and 40% of children responded with a ≥ 4-fold increase of S. sonnei LPS-specific IgA antibody in lymphocyte supernatant (ALS). At the same dose, 63% of adults and 70% of children seroconverted with IgA to LPS, while in placebo, 33% of adults and 18% of children seroconverted. Both the vaccinees and placebos responded with fecal IgA to LPS, indicating persistent exposure to Shigella infections. In conclusion, WRSS1 was found safe up to 106 CFU dose and immunogenic in adults and children in Bangladesh. These data indicate that live, oral Shigella vaccine candidates, including WRSS1 can potentially be evaluated in toddlers and infants (<2 years of age), who comprise the target population in an endemic environment.
KW - Bangladesh
KW - Shigella sonnei vaccine
KW - WRSS1
KW - adult
KW - children
KW - endemic region
KW - phase I trial
UR - http://www.scopus.com/inward/record.url?scp=85063125869&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063125869&partnerID=8YFLogxK
U2 - 10.1080/21645515.2019.1575165
DO - 10.1080/21645515.2019.1575165
M3 - Article
C2 - 30794051
AN - SCOPUS:85063125869
SN - 2164-5515
VL - 15
SP - 1326
EP - 1337
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 6
ER -