A Human Challenge Study to Assess Protection of a Shigella Tetravalent Bioconjugate Vaccine

Summary

In this challenge study, the bioconjugate candidate vaccine Shigella4V2 will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella sonnei strain compared to participants receiving placebo.

Timeline

Start

2024-11-12

Primary completion

2026-04-14

Completion

2026-09

Publications

• Background Clarkson KA, Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer A, Porter CK, Chakraborty S, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts HP, Feijoo B, Halpern J, Sack D, Riddle MS, Fonck VG, Kaminski RW. Immune response characterization in a human challenge study with a Shigella flexneri 2a bioconjugate vaccine. EBioMedicine. 2021 Apr;66:103308. doi: 10.1016/j.ebiom.2021.103308. Epub 2021 Apr 1.
• Background Cohen D, Ashkenazi S, Green MS, Gdalevich M, Robin G, Slepon R, Yavzori M, Orr N, Block C, Ashkenazi I, Shemer J, Taylor DN, Hale TL, Sadoff JC, Pavliakova D, Schneerson R, Robbins JB. Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults. Lancet. 1997 Jan 18;349(9046):155-9. doi: 10.1016/S0140-6736(96)06255-1.
• 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 Frenck RW Jr, Dickey M, Suvarnapunya AE, Chandrasekaran L, Kaminski RW, Clarkson KA, McNeal M, Lynen A, Parker S, Hoeper A, Mani S, Fix A, Maier N, Venkatesan MM, Porter CK. Establishment of a Controlled Human Infection Model with a Lyophilized Strain of Shigella sonnei 53G. mSphere. 2020 Sep 23;5(5):e00416-20. doi: 10.1128/mSphere.00416-20.
• Background Hausdorff WP, Anderson JD 4th, Bagamian KH, Bourgeois AL, Mills M, Sawe F, Scheele S, Talaat K, Giersing BK. Vaccine value profile for Shigella. Vaccine. 2023 Nov 3;41 Suppl 2:S76-S94. doi: 10.1016/j.vaccine.2022.12.037. Epub 2023 Oct 10.
• Background Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi AKM. Shigellosis. Lancet. 2018 Feb 24;391(10122):801-812. doi: 10.1016/S0140-6736(17)33296-8. Epub 2017 Dec 16.
• Background MacLennan CA, Aguilar AO, Steele AD. Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview. Clin Infect Dis. 2019 Dec 9;69(Suppl 8):S577-S579. doi: 10.1093/cid/ciz886.
• Background MacLennan CA, Grow S, Ma LF, Steele AD. The Shigella Vaccines Pipeline. Vaccines (Basel). 2022 Aug 24;10(9):1376. doi: 10.3390/vaccines10091376.
• Background Martin P, Alaimo C. The Ongoing Journey of a Shigella Bioconjugate Vaccine. Vaccines (Basel). 2022 Jan 29;10(2):212. doi: 10.3390/vaccines10020212.
• 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 Porter CK, Thura N, Ranallo RT, Riddle MS. The Shigella human challenge model. Epidemiol Infect. 2013 Feb;141(2):223-32. doi: 10.1017/S0950268812001677. Epub 2012 Aug 21.
• Background Porter CK, Lynen A, Riddle MS, Talaat K, Sack D, Gutierrez RL, McKenzie R, DeNearing B, Feijoo B, Kaminski RW, Taylor DN, Kirkpatrick BD, Bourgeois AL. Clinical endpoints in the controlled human challenge model for Shigella: A call for standardization and the development of a disease severity score. PLoS One. 2018 Mar 28;13(3):e0194325. doi: 10.1371/journal.pone.0194325. eCollection 2018.
• 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.

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