Study to Expand Safety and Immunogenicity Data With Shigella Bioconjugate Vaccine (Shigella4V2) in 9-month-old Infants.

Summary

In this study, the second-generation tetravalent bioconjugate candidate vaccine Shigella4V2 will be tested to confirm data on its safety and immunogenicity in infants and to identify the best dose of Shigella4V2 in 9-month-old infants.

Timeline

Start

2025-04-07

Primary completion

2025-08-27

Completion

2026-01-22

Publications

• Background Khalil IA, Troeger C, Blacker BF, Rao PC, Brown A, Atherly DE, Brewer TG, Engmann CM, Houpt ER, Kang G, Kotloff KL, Levine MM, Luby SP, MacLennan CA, Pan WK, Pavlinac PB, Platts-Mills JA, Qadri F, Riddle MS, Ryan ET, Shoultz DA, Steele AD, Walson JL, Sanders JW, Mokdad AH, Murray CJL, Hay SI, Reiner RC Jr. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016. Lancet Infect Dis. 2018 Nov;18(11):1229-1240. doi: 10.1016/S1473-3099(18)30475-4. Epub 2018 Sep 25.
• Background Bengtsson RJ, Simpkin AJ, Pulford CV, Low R, Rasko DA, Rigden DJ, Hall N, Barry EM, Tennant SM, Baker KS. Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs. Nat Microbiol. 2022 Feb;7(2):251-261. doi: 10.1038/s41564-021-01054-z. Epub 2022 Jan 31.
• Background GBD 2015 LRI Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017 Nov;17(11):1133-1161. doi: 10.1016/S1473-3099(17)30396-1. Epub 2017 Aug 23.
• Background Luby SP, Rahman M, Arnold BF, Unicomb L, Ashraf S, Winch PJ, Stewart CP, Begum F, Hussain F, Benjamin-Chung J, Leontsini E, Naser AM, Parvez SM, Hubbard AE, Lin A, Nizame FA, Jannat K, Ercumen A, Ram PK, Das KK, Abedin J, Clasen TF, Dewey KG, Fernald LC, Null C, Ahmed T, Colford JM Jr. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial. Lancet Glob Health. 2018 Mar;6(3):e302-e315. doi: 10.1016/S2214-109X(17)30490-4. Epub 2018 Jan 29.
• Background Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013 Jul 20;382(9888):209-22. doi: 10.1016/S0140-6736(13)60844-2. Epub 2013 May 14.
• Background Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, Adegbola RA, Alonso PL, Breiman RF, Faruque AS, Saha D, Sow SO, Sur D, Zaidi AK, Biswas K, Panchalingam S, Clemens JD, Cohen D, Glass RI, Mintz ED, Sommerfelt H, Levine MM. The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study. Clin Infect Dis. 2012 Dec;55 Suppl 4(Suppl 4):S232-45. doi: 10.1093/cid/cis753.
• Background O'Reilly CE, Jaron P, Ochieng B, Nyaguara A, Tate JE, Parsons MB, Bopp CA, Williams KA, Vinje J, Blanton E, Wannemuehler KA, Vulule J, Laserson KF, Breiman RF, Feikin DR, Widdowson MA, Mintz E. Risk factors for death among children less than 5 years old hospitalized with diarrhea in rural western Kenya, 2005-2007: a cohort study. PLoS Med. 2012;9(7):e1001256. doi: 10.1371/journal.pmed.1001256. Epub 2012 Jul 3.
• Background Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, Antonio M, Hossain A, Mandomando I, Ochieng JB, Oundo JO, Qureshi S, Ramamurthy T, Tamboura B, Adegbola RA, Hossain MJ, Saha D, Sen S, Faruque AS, Alonso PL, Breiman RF, Zaidi AK, Sur D, Sow SO, Berkeley LY, O'Reilly CE, Mintz ED, Biswas K, Cohen D, Farag TH, Nasrin D, Wu Y, Blackwelder WC, Kotloff KL, Nataro JP, Levine MM. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis. 2014 Oct;59(7):933-41. doi: 10.1093/cid/ciu468. Epub 2014 Jun 23.
• Background Samandari T, Okafor CN. Shigellosis. 2025 Dec 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK482337/
• Background Khan WA, Griffiths JK, Bennish ML. Gastrointestinal and extra-intestinal manifestations of childhood shigellosis in a region where all four species of Shigella are endemic. PLoS One. 2013 May 17;8(5):e64097. doi: 10.1371/journal.pone.0064097. Print 2013.
• Background Shad AA, Shad WA. Shigella sonnei: virulence and antibiotic resistance. Arch Microbiol. 2021 Jan;203(1):45-58. doi: 10.1007/s00203-020-02034-3. Epub 2020 Sep 14.
• Background Puzari M, Sharma M, Chetia P. Emergence of antibiotic resistant Shigella species: A matter of concern. J Infect Public Health. 2018 Jul-Aug;11(4):451-454. doi: 10.1016/j.jiph.2017.09.025. Epub 2017 Oct 20.
• Background Riddle MS, Kaminski RW, Di Paolo C, Porter CK, Gutierrez RL, Clarkson KA, Weerts HE, Duplessis C, Castellano A, Alaimo C, Paolino K, Gormley R, Gambillara Fonck V. Safety and Immunogenicity of a Candidate Bioconjugate Vaccine against Shigella flexneri 2a Administered to Healthy Adults: a Single-Blind, Randomized Phase I Study. Clin Vaccine Immunol. 2016 Dec 5;23(12):908-917. doi: 10.1128/CVI.00224-16. Print 2016 Dec.
• Background Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer AM, Kaminski RW, Porter CK, Chakraborty S, Clarkson KA, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts H, Feijoo BL, Halpern J, Sack D, Riddle MS, Fonck VG. Human challenge study with a Shigella bioconjugate vaccine: Analyses of clinical efficacy and correlate of protection. EBioMedicine. 2021 Apr;66:103310. doi: 10.1016/j.ebiom.2021.103310. Epub 2021 Apr 13.
• Background Cohen D, Ashkenazi S, Green M, Lerman Y, Slepon R, Robin G, Orr N, Taylor DN, Sadoff JC, Chu C, Shiloach J, Schneerson R, Robbins JB. Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers. Infect Immun. 1996 Oct;64(10):4074-7. doi: 10.1128/iai.64.10.4074-4077.1996.
• Background Passwell JH, Ashkenazi S, Banet-Levi Y, Ramon-Saraf R, Farzam N, Lerner-Geva L, Even-Nir H, Yerushalmi B, Chu C, Shiloach J, Robbins JB, Schneerson R; Israeli Shigella Study Group. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children. Vaccine. 2010 Mar 2;28(10):2231-2235. doi: 10.1016/j.vaccine.2009.12.050. Epub 2010 Jan 5.
• Background Ashkenazi S, Passwell JH, Harlev E, Miron D, Dagan R, Farzan N, Ramon R, Majadly F, Bryla DA, Karpas AB, Robbins JB, Schneerson R. Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. J Infect Dis. 1999 Jun;179(6):1565-8. doi: 10.1086/314759.

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Indications