Development of a Shigella conjugate vaccine targeting Shigella flexneri 6 that is immunogenic and provides protection against virulent challenge.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam, The Netherlands : Elsevier Science
      Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1983-
    • Subject Terms:
      Shigella flexneri*/immunology ; Shigella Vaccines*/immunology ; Shigella Vaccines*/administration & dosage ; Dysentery, Bacillary*/prevention & control ; Dysentery, Bacillary*/immunology ; Antibodies, Bacterial*/blood ; Antibodies, Bacterial*/immunology ; Vaccines, Conjugate*/immunology ; Vaccines, Conjugate*/administration & dosage ; Immunoglobulin G*/blood ; Immunoglobulin G*/immunology ; O Antigens*/immunology; Animals ; Mice ; Humans ; Female ; Mice, Inbred BALB C ; Immunoglobulin M/immunology ; Immunoglobulin M/blood ; Serogroup ; Lipopolysaccharides/immunology
    • Abstract:
      Immunity protective against shigella infection targets the bacterial O-specific polysaccharide (OSP) component of lipopolysaccharide. A multivalent shigella vaccine would ideally target the most common global Shigella species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. We previously reported development of shigella conjugate vaccines (SCVs) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using a platform squaric acid chemistry conjugation approach and carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. Here we report development of a SCV targeting S. flexneri 6 (SCV-Sf6) using the same platform approach. We demonstrated that SCV-Sf6 was recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG and IgM responses, as well as rTTHc-specific IgG responses. Immune responses were increased when administered with aluminum phosphate adjuvant. Vaccination induced bactericidal antibody responses against S. flexneri 6, and vaccinated animals were protected against lethal challenge with virulent S. flexneri 6. Our results assist in the development of a multivalent vaccine protective against shigellosis.
      Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Kaminski reports a relationship with Latham BioPharm Group that includes: employment. Edward T Ryan has patent ##9,616,139 issued to Massachusetts General Hospital.
      (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
    • References:
      Pediatr Clin North Am. 2017 Aug;64(4):799-814. (PMID: 28734511)
      J Clin Microbiol. 1991 Feb;29(2):386-9. (PMID: 1706731)
      Clin Vaccine Immunol. 2016 Jul 05;23(7):564-75. (PMID: 27146000)
      Vaccine. 2015 Aug 26;33(36):4594-601. (PMID: 26162850)
      mSphere. 2022 Jun 29;7(3):e0102021. (PMID: 35611657)
      ACS Cent Sci. 2022 Apr 27;8(4):449-460. (PMID: 35559427)
      EBioMedicine. 2021 Apr;66:103343. (PMID: 33873142)
      Clin Vaccine Immunol. 2016 Dec 5;23(12):908-917. (PMID: 27581434)
      Lancet. 1997 Jan 18;349(9046):155-9. (PMID: 9111538)
      Epidemiol Infect. 2014 Dec;142(12):2583-94. (PMID: 24559503)
      Am J Trop Med Hyg. 2021 Apr 19;104(6):2024-2030. (PMID: 33872211)
      Bull World Health Organ. 1999;77(8):651-66. (PMID: 10516787)
      Vaccine. 2021 Nov 16;39(47):6936-6946. (PMID: 34716040)
      Infect Immun. 2000 Dec;68(12):6624-32. (PMID: 11083774)
      Vaccine. 2011 Feb 1;29(6):1347-54. (PMID: 21040694)
      Nat Rev Microbiol. 2007 Jul;5(7):540-53. (PMID: 17558427)
      Vaccine. 2018 Aug 6;36(32 Pt B):4880-4889. (PMID: 30037478)
      Clin Vaccine Immunol. 2014 Mar;21(3):366-82. (PMID: 24403527)
      Vaccines (Basel). 2021 Dec 28;10(1):. (PMID: 35062694)
      Clin Infect Dis. 2014 Oct;59(7):933-41. (PMID: 24958238)
      Hum Vaccin. 2007 Nov-Dec;3(6):268-75. (PMID: 17938573)
      EBioMedicine. 2017 Aug;22:164-172. (PMID: 28735965)
      Pediatr Infect Dis J. 2003 Aug;22(8):701-6. (PMID: 12913770)
      Lancet Infect Dis. 2021 Apr;21(4):546-558. (PMID: 33186516)
      Vaccines (Basel). 2020 Apr 03;8(2):. (PMID: 32260067)
      Clin Vaccine Immunol. 2016 Apr 04;23(4):315-25. (PMID: 26865592)
      mSphere. 2018 Mar 28;3(2):. (PMID: 29600284)
      Vaccines (Basel). 2022 Apr 24;10(5):. (PMID: 35632431)
      PLoS Negl Trop Dis. 2014 Feb 06;8(2):e2683. (PMID: 24516685)
      Vaccine. 2023 Jul 31;41(34):4967-4977. (PMID: 37400283)
      Carbohydr Res. 2010 Jul 19;345(11):1600-8. (PMID: 20542498)
      Vaccine. 2010 Mar 2;28(10):2231-2235. (PMID: 20056180)
      Vaccines (Basel). 2022 Aug 24;10(9):. (PMID: 36146457)
      Front Immunol. 2017 Dec 22;8:1884. (PMID: 29375556)
      Chemistry. 2019 Oct 8;25(56):12946-12956. (PMID: 31306528)
      J Clin Microbiol. 1988 Jul;26(7):1343-8. (PMID: 3045151)
      Vaccines (Basel). 2022 Mar 07;10(3):. (PMID: 35335035)
      PLoS Negl Trop Dis. 2015 Jul 08;9(7):e0003881. (PMID: 26154421)
      Hum Vaccin Immunother. 2019;15(6):1326-1337. (PMID: 30794051)
      Chembiochem. 2017 Apr 18;18(8):799-815. (PMID: 28182850)
      Glycobiology. 2011 Oct;21(10):1362-72. (PMID: 21752864)
      Lancet. 2016 Oct 8;388(10053):1459-1544. (PMID: 27733281)
      Bioconjug Chem. 2016 Apr 20;27(4):883-92. (PMID: 26918643)
      Bioconjug Chem. 2011 Oct 19;22(10):2179-85. (PMID: 21899371)
      Lancet Infect Dis. 2018 Nov;18(11):1229-1240. (PMID: 30266330)
      Vaccine. 2017 Sep 5;35(37):4990-4996. (PMID: 28797729)
      Anal Biochem. 1988 Dec;175(2):525-30. (PMID: 3239778)
      J Infect Dis. 1997 May;175(5):1128-33. (PMID: 9129076)
      Clin Vaccine Immunol. 2012 Nov;19(11):1712-21. (PMID: 22993410)
      J Infect Dis. 1988 May;157(5):1068-71. (PMID: 3283258)
      Infect Immun. 2004 Feb;72(2):923-30. (PMID: 14742537)
      PLoS Negl Trop Dis. 2021 Oct 13;15(10):e0009826. (PMID: 34644291)
    • Grant Information:
      R01 AI155414 United States AI NIAID NIH HHS; R01 AI177075 United States AI NIAID NIH HHS; R01 AI106878 United States AI NIAID NIH HHS; D43 TW005572 United States TW FIC NIH HHS; R56 AI106878 United States AI NIAID NIH HHS; R37 AI106878 United States AI NIAID NIH HHS; K43 TW010362 United States TW FIC NIH HHS
    • Contributed Indexing:
      Keywords: Conjugate; Immunity; S. flexneri 6; Shigella; Shigellosis; Squaric acid; Vaccine
    • Accession Number:
      0 (Shigella Vaccines)
      0 (Antibodies, Bacterial)
      0 (Vaccines, Conjugate)
      0 (Immunoglobulin G)
      0 (O Antigens)
      0 (Immunoglobulin M)
      0 (Lipopolysaccharides)
    • Publication Date:
      Date Created: 20240901 Date Completed: 20240913 Latest Revision: 20240921
    • Publication Date:
      20250114
    • Accession Number:
      PMC11409015
    • Accession Number:
      10.1016/j.vaccine.2024.126263
    • Accession Number:
      39217775