A bivalent vaccine confers immunogenicity and protection against Shigella flexneri and enterotoxigenic Escherichia coli infections in mice

Bolick, David T.; Ledwaba, Solanka Ellen; Kolling, Glynis L.; Costa, Deiziane Viana da Silva; Oriá, Reinaldo B.; Lima, Aldo Ângelo Moreira; Barry, Eileen M.; Guerrant, Richard L.

doi:10.1038/s41541-020-0180-y

Cited by 22 publications

(18 citation statements)

References 21 publications

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“…Intermediate between Campylobacter and ETEC infections, Shigella infections show the greatest effect on acute weight loss and diarrhea over 1–3 days after infection, but these clinical effects, like fecal pathogen shedding, are transient unless the mice are zinc-deficient. 53 , 54 …”

Section: Roles Of Specific Pathogensmentioning

confidence: 99%

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

2021

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Developing effective therapeutics or preventive interventions for important health threats is greatly enhanced whenever accessible models can enable the assessment of clinically important outcomes. While no non-human model is ever perfect, inexpensive in vivo small animal models in such as mice are often of great help in assessing the relevant efficacy of potential interventions. In addition to acute diarrhea, the long-term growth and developmental effects of enteric infections, with or without overt diarrhea, are increasingly recognized. To address these diverse effects, inexpensive animal models are proving to be very helpful. Herein, we review the major clinical concerns with enteric parasitic and bacterial infections that are extremely common worldwide, especially in vulnerable young children living in impoverished areas, and the recently published murine models of these infections and their outcomes. We find that common dietary deficiencies seen in children in developing areas have striking effects on diarrhea and enteropathy outcomes in mice. However, these effects differ with different pathogens. Specifically, the effects of protein or zinc deficiency differ considerably with different major protozoal and bacterial pathogens, suggesting different pathogenetic pathways and intervention effects. The pathogens reviewed are the seven top parasitic and bacterial pathogens seen in children, namely, Cryptosporidium , Giardia , Campylobacter , Shigella , enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), and enteropathogenic E. coli (EPEC).

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Section: Roles Of Specific Pathogensmentioning

confidence: 99%

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

2021

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“…Whether the homology between the two organisms will be sufficient with antitoxin immunity against all major clinical strains of ETEC is unknown. However, some data reported by Medeiros et al [ 58 ] indicate that at least some protection against ETEC is obtained with the CVD1208S strain not expressing CFs, suggesting some level of conserved protection in mice from Shigella antigens.…”

Section: Etec Componentmentioning

confidence: 98%

“…A vaccine consisting of four strains of Shigella attenuated by deletion in the guaBA 196 operon (see above under Shigella component) wasconstructed as a Shigella -ETEC bivalent hybrid vaccine expressing major CFA/ICS antigens of ETEC, along with labile toxin B subunit (LTB) and a stable toxin (ST) toxoid [ 57 ]. A prototype of this vaccine, CVD1208S-122, was recently tested in an antibiotic treated mouse model and protection against disease was seen following oral challenge with ETEC or Shigella [ 58 ].…”

Section: Etec Componentmentioning

confidence: 99%

“…The guaBA Shigella −ETEC hybrid 1208-122 should provide effective coverage against both Shigella and ETEC, relying on antigens that have been well established to protect [ 57 ]. A prototype of this candidate, S. flexneri 2a expressing CFA/I and LT, protected orally challenged mice against ETEC and Shigella [ 58 ], and may enter Phase 1 evaluation in 2021 ( , accessed on 1 May 2021). This approach demonstrates the use of expression of heterologous antigens to broaden coverage, which could also be applied to conserved Campylobacter antigens.…”

Section: Multi-pathogen Strategiesmentioning

confidence: 99%

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Vaccines for Protecting Infants from Bacterial Causes of Diarrheal Disease

et al. 2021

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The global diarrheal disease burden for Shigella, enterotoxigenic Escherichia coli (ETEC), and Campylobacter is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. All three of these pathogens contribute to growth stunting and have demonstrated increasing resistance to antimicrobial agents. Several combinations of antigens are now recognized that could be effective for inducing protective immunity against each of the three target pathogens in a single vaccine for oral administration or parenteral injection. The vaccine combinations proposed here would result in a final product consistent with the World Health Organization’s (WHO) preferred product characteristics for ETEC and Shigella vaccines, and improve the vaccine prospects for support from Gavi, the Vaccine Alliance, and widespread uptake by low- and middle-income countries’ (LMIC) public health stakeholders. Broadly protective antigens will enable multi-pathogen vaccines to be efficiently developed and cost-effective. This review describes how emerging discoveries for each pathogen component of the target trio could be used to make vaccines, which could help reduce a major cause of poor health, reduced cognitive development, lost economic productivity, and poverty in many parts of the world.

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“…Also, due to the emergence of globally antibiotic resistance against Shigella, preventive measures are needed. Currently, there is no licensed vaccine against shigellosis, while numerous vaccine candidates are in different trial steps (Frenck Jr et al 2018;Gilavand et al 2020;Medeiros et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Identification and evaluation of novel vaccine candidates against Shigella flexneri through reverse vaccinology approach

Hajialibeigi

Amani

Gargari

2021

Appl Microbiol Biotechnol

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Shigellosis is a significant type of diarrhea that causes 160,000 deaths annually in a global scale. The mortality occurs mainly in children less than 5 years of age. No licensed vaccine is available, and conventional efforts for developing an effective and safe vaccine against shigellosis have not been succeeded yet. The reverse vaccinology is a novel promising method that screens genome or proteome of an organism for finding new vaccine candidates. In this study, through reverse vaccinology approach, new vaccine candidates against Shigella flexneri were identified and experimentally evaluated. Proteomes of S. flexneri were obtained from UniProt, and then outer membrane and extracellular proteins were predicted and selected for the evaluation of transmembrane domains, protein conservation, host homology, antigenicity, and solubility. From 103 proteins, 7 high-scored proteins were introduced as novel vaccine candidates, and after Band T-cell epitope prediction, the best protein was selected for experimental studies. Recombinant protein was expressed, purified, and injected to BALB/c mice. The adhesion inhibitory effect of sera was also studied. The immunized mice demonstrated full protection against the lethal dose challenge. The sera remarkably inhibited S. flexneri adhesion to Caco-2 epithelial cells. The results indicate that identified antigen can serve for vaccine development against shigellosis and support reverse vaccinology for discovering novel effective antigens. Key points • Seven Shigella new antigens were identified by reverse vaccinology (RV) approach. • The best antigen experimented demonstrated full protection against lethal dose. • In vivo results verified RV analyses and suggest FimG as a new potent vaccine candidate.

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A bivalent vaccine confers immunogenicity and protection against Shigella flexneri and enterotoxigenic Escherichia coli infections in mice

Cited by 22 publications

References 21 publications

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

Vaccines for Protecting Infants from Bacterial Causes of Diarrheal Disease

Identification and evaluation of novel vaccine candidates against Shigella flexneri through reverse vaccinology approach

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