AUTHOR=Kim Min Jung , Moon Young-hye , Kim Heejoo , Rho Semi , Shin Young Kee , Song Manki , Walker Richard , Czerkinsky Cecil , Kim Dong Wook , Kim Jae-Ouk 

TITLE=Cross-Protective Shigella Whole-Cell Vaccine With a Truncated O-Polysaccharide Chain

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02609

DOI=10.3389/fmicb.2018.02609

ISSN=1664-302X

ABSTRACT=<p><italic>Shigella</italic> is a highly prevalent bacterium causing acute diarrhea and dysentery in developing countries. <italic>Shigella</italic> infections are treated with antibiotics but Shigellae are increasingly resistant to these drugs. Vaccination can be a countermeasure against emerging antibiotic-resistant shigellosis. Because of the structural variability in Shigellae O-antigen polysaccharides (Oag), cross-protective <italic>Shigella</italic> vaccines cannot be derived from single serotype-specific Oag. We created an attenuated <italic>Shigella flexneri</italic> 2a strain with one rather than multiple Oag units by disrupting the Oag polymerase gene (Δ<italic>wzy</italic>), which broadened protective immunogenicity by exposing conserved surface proteins. Inactivated Δ<italic>wzy</italic> mutant cells combined with <italic>Escherichia coli</italic> double mutant LT(R192G/L211A) as adjuvant, induced potent antibody responses to outer membrane protein PSSP-1, and type III secretion system proteins IpaB and IpaC. Intranasal immunization with the vaccine preparation elicited cross-protective immunity against <italic>S. flexneri</italic> 2a, <italic>S. flexneri</italic> 3a, <italic>S. flexneri</italic> 6, and <italic>Shigella sonnei</italic> in a mouse pneumonia model. Thus, <italic>S. flexneri</italic> 2a Δ<italic>wzy</italic> represents a promising candidate strain for a universal <italic>Shigella</italic> vaccine.</p>