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
  • [1] Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children
    Ashkenazi, S
    Passwell, JH
    Harlev, E
    Miron, D
    Dagan, R
    Farzan, N
    Ramon, R
    Majadly, F
    Bryla, DA
    Karpas, AB
    Robbins, JB
    Schneerson, R
    JOURNAL OF INFECTIOUS DISEASES, 1999, 179 (06): : 1565 - 1568
  • [2] O-Acetylation in the O-specific polysaccharide isolated from Shigella flexneri serotype 2a
    Kubler-Kielb, Joanna
    Vinogradov, Evgeny
    Chu, Chiayung
    Schneerson, Rachel
    CARBOHYDRATE RESEARCH, 2007, 342 (3-4) : 643 - 647
  • [3] STRUCTURAL STUDIES ON O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-FLEXNERI SEROTYPE-6
    KATZENELLENBOGEN, E
    MULCZYK, M
    ROMANOWSKA, E
    EUROPEAN JOURNAL OF BIOCHEMISTRY, 1976, 61 (01): : 191 - 197
  • [4] Total synthesis of a tetra- and two pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a
    Mulard, LA
    Guerreiro, C
    TETRAHEDRON, 2004, 60 (11) : 2475 - 2488
  • [5] ACETYLATION OF O-SPECIFIC LIPOPOLYSACCHARIDES FROM SHIGELLA-FLEXNERI 3A AND SHIGELLA-FLEXNERI 2A OCCURS IN ESCHERICHIA-COLI K-12 CARRYING CLONED SHIGELLA-FLEXNERI 3A AND SHIGELLA-FLEXNERI 2A RFB GENES
    YAO, ZJ
    LIU, HM
    VALVANO, MA
    JOURNAL OF BACTERIOLOGY, 1992, 174 (23) : 7500 - 7508
  • [6] SYNTHESIS OF THE O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-FLEXNERI
    KOCHETKOV, NK
    BYRAMOVA, NE
    TSVETKOV, YE
    BACKINOWSKY, LV
    TETRAHEDRON, 1985, 41 (16) : 3363 - 3375
  • [7] Synthesis of ligands related to the O-specific polysaccharides of Shigella flexneri serotype 2a and Shigella flexneri serotype 5a part 5 -: Linear synthesis of the methyl glycosides of tetra and pentasaccharide fragments specific for the Shigella flexneri serotype 2a O-antigen
    Costachel, C
    Sansonetti, PJ
    Mulard, LA
    JOURNAL OF CARBOHYDRATE CHEMISTRY, 2000, 19 (09) : 1131 - 1150
  • [8] Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates
    Kubler-Kielb, Joanna
    Vinogradov, Evgeny
    Mocca, Christopher
    Pozsgay, Vince
    Coxon, Bruce
    Robbins, John B.
    Schneerson, Rachel
    CARBOHYDRATE RESEARCH, 2010, 345 (11) : 1600 - 1608
  • [9] Convergent synthesis of the methyl glycosides of a tetra- and a pentasaccharide fragment of the Shigella flexneri serotype 2a O-specific polysaccharide
    Segat-Dioury, F
    Mulard, LA
    TETRAHEDRON-ASYMMETRY, 2002, 13 (20) : 2211 - 2222
  • [10] Synthesis of the monosaccharide units of the O-specific polysaccharide of Shigella sonnei
    Medgyes, A
    Farkas, E
    Liptak, A
    Pozsgay, V
    TETRAHEDRON, 1997, 53 (12) : 4159 - 4178