Abstract
Shigella is a highly prevalent bacterium causing acute diarrhea and dysentery in developing countries. Shigella 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 Shigella vaccines cannot be derived from single serotype-specific Oag. We created an attenuated Shigella flexneri 2a strain with one rather than multiple Oag units by disrupting the Oag polymerase gene (Δwzy), which broadened protective immunogenicity by exposing conserved surface proteins. Inactivated Δwzy mutant cells combined with Escherichia coli 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 S. flexneri 2a, S. flexneri 3a, S. flexneri 6, and Shigella sonnei in a mouse pneumonia model. Thus, S. flexneri 2a Δwzy represents a promising candidate strain for a universal Shigella vaccine.
Highlights
Shigellosis is one of the major enteric pathogens and is globally associated with 164,300 diarrheal deaths in all age groups including 54,900 diarrheal deaths in children younger than 5 years (Lozano et al, 2012; Liu et al, 2016; Hosangadi et al, 2018)
We found that pan Shigella surface protein-1 (PSSP-1)-specific antibodies did not bind IcsP on Shigella cells, which was consistent with another report that LPS O-antigen polysaccharides (Oag) of gram-negative bacteria masks other surface antigens, such as IcsP (S. flexneri), by preventing antibody access
We observed that PSSP-1-specific-antibodies did not bind to the bacterial surface of wild type (WT) S. flexneri 2a 2457T, whereas the same anti-serum could bind to wzy
Summary
Shigellosis is one of the major enteric pathogens and is globally associated with 164,300 diarrheal deaths in all age groups including 54,900 diarrheal deaths in children younger than 5 years (Lozano et al, 2012; Liu et al, 2016; Hosangadi et al, 2018). It is responsible for long-term health and cognitive defects associated with stunting (Niehaus et al, 2002; Guerrant et al, 2008; Walker, 2015). Antibiotics can effectively treat shigellosis but the emergence of antibiotic resistance makes
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