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

Autor: Kelly M; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: mkell22@mgh.harvard.edu., Janardhanan J; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: jjanardhanan@mgh.harvard.edu., Wagh C; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: cwagh@mgh.harvard.edu., Verma S; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: sverma5@mgh.harvard.edu., Charles RC; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: rcharles@mgh.harvard.edu., Leung DT; Division of Infectious Diseases, University of Utah, Salt Lake City, UT, USA. Electronic address: Daniel.Leung@utah.edu., Kamruzzaman M; icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh., Pansuriya RK; International Vaccine Institute, Seoul, South Korea. Electronic address: ruchir.pansuriya@ivi.int., Chowdhury F; icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh. Electronic address: fchowdhury@icddrb.org., Vann WF; Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address: Willie.Vann@fda.hhs.gov., Kaminski RW; Latham BioPharm Group, Cambridge, MA, USA. Electronic address: rkaminski@lathambiopharm.com., Khan AI; icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh. Electronic address: ashrafk@icddrb.org., Bhuiyan TR; icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh. Electronic address: taufiqur@icddrb.org., Qadri F; icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh. Electronic address: fqadri@icddrb.org., Kováč P; NIDDK, LBC, National Institutes of Health, Bethesda, MD, USA. Electronic address: kovac@niddk.nih.gov., Xu P; NIDDK, LBC, National Institutes of Health, Bethesda, MD, USA. Electronic address: peng.xu@nih.gov., Ryan ET; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: etryan@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Oct 24; Vol. 42 (24), pp. 126263. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.vaccine.2024.126263
Abstrakt: 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.)
Databáze: MEDLINE
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