Evaluation of a Quadrivalent Shigella flexneri Serotype 2a, 3a, 6, and Shigella sonnei O-Specific Polysaccharide and IpaB MAPS Vaccine

被引:0
|
作者
Boerth, Emily M. [1 ]
Gong, Joyce [1 ]
Roffler, Becky [1 ]
Hancock, Zoe [1 ]
Berger, Lydia [1 ]
Song, Boni [1 ]
Malley, Sasha F. [1 ]
Maclennan, Calman A. [2 ]
Zhang, Fan [1 ]
Malley, Richard [1 ]
Lu, Ying-Jie [1 ]
机构
[1] Harvard Med Sch, Div Infect Dis, Boston Childrens Hosp, Boston, MA 02115 USA
[2] Global Hlth Bill & Melinda Gates Fdn, Enter & Diarrheal Dis, 500 5th Ave N, Seattle, WA 98109 USA
关键词
<italic>Shigella</italic>; MAPS vaccine; OSP; IpaB; quadrivalent; INVASION PLASMID; HEALTHY-ADULTS; LIPOPOLYSACCHARIDE; ANTIGENS; IMMUNOGENICITY; ACETYLATION; CONJUGATE; RESPONSES; CHILDREN; EFFICACY;
D O I
10.3390/vaccines12101091
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective Shigella vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent Salmonella MAPS vaccines that induce functional antibodies against Salmonella components. Methods: In this work, we detail the development of several monovalent vaccines using O-specific polysaccharides (OSPs) from four dominant serotypes, S. flexneri 2a, 3a, and 6, and S. sonnei. We tested several rhizavidin (rhavi) fusion proteins and selected a Shigella-specific protein IpaB. Quadrivalent MAPS were made with Rhavi-IpaB protein and tested in rabbits for immunogenicity. Results: Individual MAPS vaccines generated robust, functional antibody responses against both IpaB and the individual OSP component. Antibodies to IpaB were effective across Shigella serotypes. We also demonstrate that the OSP antibodies generated are specific to each homologous Shigella O type by performing ELISA and bactericidal assays. We combined the components of each MAPS vaccine to formulate a quadrivalent MAPS vaccine which elicited similar antibody and bactericidal responses compared to their monovalent counterparts. Finally, we show that the quadrivalent MAPS immune sera are functional against several clinical isolates of the serotypes used in the vaccine. Conclusions: This quadrivalent MAPS Shigella vaccine is immunogenicity and warrants further study.
引用
收藏
页数:11
相关论文
共 50 条
  • [31] THE CORE STRUCTURE OF SHIGELLA-SONNEI LIPOPOLYSACCHARIDE AND THE LINKAGE BETWEEN O-SPECIFIC POLYSACCHARIDE AND THE CORE REGION
    GAMIAN, A
    ROMANOWSKA, E
    EUROPEAN JOURNAL OF BIOCHEMISTRY, 1982, 129 (01): : 105 - 109
  • [32] Synthesis and NMR study of a linear pentasaccharide fragment of the Shigella flexneri 5a O-specific polysaccharide
    Mulard, LA
    Clément, MJ
    Segat-Dioury, F
    Delepierre, M
    TETRAHEDRON, 2002, 58 (13) : 2593 - 2604
  • [33] The Shigella flexneri serotype Y vaccine candidate SFL124 originated from a serotype 2a background
    Roberts, F
    Jennison, AV
    Verma, NK
    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 2005, 45 (02): : 285 - 289
  • [34] Synthesis of the methyl glycoside of a branched octasaccharide fragment specific for the Shigella flexneri serotype 2a O-antigen
    Bélot, F
    Costachel, C
    Wright, K
    Phalipon, A
    Mulard, LA
    TETRAHEDRON LETTERS, 2002, 43 (46) : 8215 - 8218
  • [35] Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a
    Hlozek, Jason
    Owen, Sara
    Ravenscroft, Neil
    Kuttel, Michelle M.
    VACCINES, 2020, 8 (04) : 1 - 17
  • [36] Genomic, transcriptomic, and phenotypic differences among archetype Shigella flexneri strains of serotypes 2a, 3a, and 6
    Gabor, Caitlin E.
    Hazen, Tracy H.
    Delaine-Elias, BreOnna C.
    Rasko, David A.
    Barry, Eileen M.
    MSPHERE, 2023, 8 (06)
  • [37] Glycoconjugation of Shigella flexneri type 2a O-polysaccharide with CRM197 as a potential vaccine candidate for shigellosis
    Narayana, P. V. S. L. S. S.
    Dutta, Jayati Ray
    BIOLOGICALS, 2021, 72 : 1 - 9
  • [38] Characterization and immunogenicity of a Shigella flexneri 2a O-antigen bioconjugate vaccine candidate
    Ravenscroft, Neil
    Braun, Martin
    Schneider, Joerg
    Dreyer, Anita M.
    Wetter, Michael
    Haeuptle, Micha A.
    Kemmler, Stefan
    Steffen, Michael
    Sirena, Dominique
    Herwig, Stefan
    Carranza, Paula
    Jones, Claire
    Pollard, Andrew J.
    Wacker, Michael
    Kowarik, Michael
    GLYCOBIOLOGY, 2019, 29 (09) : 669 - 681
  • [39] Cross-reactivity of Shigella flexneri serotype 2a O antigen antibodies following immunization or infection
    VandeVerg, LL
    Bendiuk, NO
    Kotloff, K
    Marsh, MM
    Ruckert, JL
    Puryear, JL
    Taylor, DN
    Hartman, AB
    VACCINE, 1996, 14 (11) : 1062 - 1068
  • [40] Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a
    Dharmasena, Madushini N.
    Osorio, Manuel
    Takeda, Kazuyo
    Stibitz, Scott
    Kopecko, Dennis J.
    CLINICAL AND VACCINE IMMUNOLOGY, 2017, 24 (12)