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Vaccine. 2015 Jun 12;33(26):2978-83. doi: 10.1016/j.vaccine.2015.04.074. Epub 2015 Apr 30.

Whole genome analysis to detect potential vaccine-induced changes on Shigella sonnei genome.

Author information

1
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel. Electronic address: AdiB@moag.gov.il.
2
Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
3
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.

Abstract

Shigellosis or bacillary dysentery is endemic worldwide and is a significant cause of death in children less than five years of age in developing countries. There are no licensed Shigella vaccines and glycoconjugates are among the leading candidate vaccines against shigellosis today. We used whole genome sequence analysis (WGA) to find out whether immunization, with an investigational Shigella sonnei glycoconjugate, could induce selective pressure leading to changes in the genome of S. sonnei. An outbreak of culture-proven S. sonnei shigellosis which occurred immediately after vaccination in one of the cohorts of volunteers participating in a phase III trial of the vaccine in Israel created a unique condition in which the epidemic agent "co-existed" with the developing immune responses induced by the vaccine and natural infection among vaccinees who developed S. sonnei shigellosis. By comparing the whole genomes of S. sonnei isolated from vaccinees and from volunteers in the control group, we show at a very high sensitivity that a potent S. sonnei glycoconjugate that conferred 74% protective efficacy against the homologous disease did not induce changes in the genome of S. sonnei and in particular on the O-antigen gene cluster.

KEYWORDS:

Glycoconjugates vaccines; SNPs; Shigella sonnei; WGA

PMID:
25936664
DOI:
10.1016/j.vaccine.2015.04.074
[Indexed for MEDLINE]

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