Development of a Shigella conjugate vaccine targeting Shigella flexneri 6 that is immunogenic and provides protection against virulent challenge
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.
Authors
- Ashraful Islam Khan (ORCID: https://orcid.org/0000-0003-3751-1974)
- Peng Hui Xu (ORCID: https://orcid.org/0000-0002-9593-7167)
- Richelle C. Charles (ORCID: https://orcid.org/0000-0002-8881-1849)
- Daniel T. Leung (ORCID: https://orcid.org/0000-0001-8401-0801)
- Mohammad Kamruzzaman (ORCID: https://orcid.org/0000-0002-7954-673X)
- Fahima Chowdhury (ORCID: https://orcid.org/0000-0002-7082-0720)
- Taufiqur Rahman Bhuiyan (ORCID: https://orcid.org/0000-0003-3755-4763)
- Ruchir Kumar Pansuriya (ORCID: https://orcid.org/0000-0002-1317-3651)
- Jeshina Janardhanan (ORCID: https://orcid.org/0000-0003-4184-4325)
- Edward Thomas Ryan (ORCID: https://orcid.org/0009-0005-0169-394X)
- Robert W. Kaminski (ORCID: https://orcid.org/0000-0002-4015-5694)
- Smriti Verma (ORCID: https://orcid.org/0000-0002-3760-8090)
- Willie F. Vann (ORCID: https://orcid.org/0000-0003-4177-8874)
- Firdausi Qadri (ORCID: https://orcid.org/0000-0002-8928-9888)
- Pavol Kováč (ORCID: https://orcid.org/0000-0001-5044-3449)
- Chanchal Wagh
- Meagan Kelly
Institutions
- National Institutes of Health (US)
- International Vaccine Institute (KR)
- Center for Biologics Evaluation and Research (US)
- United States Food and Drug Administration (US)
- Harvard University (US)
- International Centre for Diarrhoeal Disease Research (BD)
- University of Utah (US)
- Massachusetts General Hospital (US)
Publication Details
- Journal
- Vaccine
- Published
- 2024-08-31
- DOI
- https://doi.org/10.1016/j.vaccine.2024.126263
- Citations
- 5
- Primary Topic
- Escherichia coli research studies
- Type
- article
- Field-Weighted Citation Impact
- 3.09
Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Fogarty International Center
- National Institute of Diabetes and Digestive and Kidney Diseases