Ruklanthi de Alwis1,2, Li Liang3, Omid Taghavian3, Emma Werner4, Hao Chung The5, Trang Nguyen Hoang Thu5, Vu Thuy Duong5, D Huw Davies3, Philip L Felgner3, Stephen Baker6. 1. Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. 2. Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore. 3. Vaccine Research & Development Center, School of Medicine, University of California Irvine, Irvine, CA, USA. 4. Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. 5. The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. 6. Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Level 5, Jeffery Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK. sgb47@medschl.cam.ac.uk.
Abstract
BACKGROUND: Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen. METHODS: Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections. RESULTS: Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody. CONCLUSIONS: These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.
BACKGROUND: Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen. METHODS: Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections. RESULTS: Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody. CONCLUSIONS: These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.
Authors: Srilatha Kuntumalla; Quanshun Zhang; John C Braisted; Robert D Fleischmann; Scott N Peterson; Arthur Donohue-Rolfe; Saul Tzipori; Rembert Pieper Journal: BMC Microbiol Date: 2011-06-24 Impact factor: 3.605
Authors: Mariaelena Caboni; Thierry Pédron; Omar Rossi; David Goulding; Derek Pickard; Francesco Citiulo; Calman A MacLennan; Gordon Dougan; Nicholas R Thomson; Allan Saul; Philippe J Sansonetti; Christiane Gerke Journal: PLoS Pathog Date: 2015-03-20 Impact factor: 6.823