Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a

Turbyfill, K. Ross; Kaminski, Robert W.; Oaks, Edwin V.

doi:10.1016/j.vaccine.2007.12.040

Cited by 42 publications

(27 citation statements)

References 30 publications

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“…It is known that in some bacterial pathogens, surface proteins, such as invasins, that are involved in direct interactions with the host system possess vaccine properties (2,38,39). In our study, we found that rEta1 induced a protection rate of 83.3% upon lethal E. tarda challenge, suggesting that rEta1 is a strong protective immunogen.…”

Section: Discussionsupporting

confidence: 49%

Edwardsiella tarda Eta1, an In Vivo -Induced Antigen That Is Involved in Host Infection

Sun

Zheng

et al. 2012

Infect Immun

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ABSTRACTEdwardsiella tarda, a Gram-negative bacterium, is a severe fish pathogen that can also infect humans. In this study, we identified, viain vivo-induced antigen technology, anE. tardaantigen, Eta1, and analyzed its function in a Japanese flounder (Paralichthys olivaceus) model. Eta1 is composed of 226 residues and shares homology with putative bacterial adhesins. Quantitative real-time reverse transcriptase (RT)-PCR analysis indicated that when culturedin vitro,eta1expression was growth phase dependent and reached maximum at mid-logarithmic phase. During infection of flounder lymphocytes,eta1expression was drastically increased at the early stage of infection. Compared to the wild type, theeta1-defective mutant, TXeta1, was unaffected in growth but exhibited attenuated overall virulence, reduced tissue dissemination and colonization capacity, and impaired ability to invade flounder lymphocytes and to block the immune response of host cells. The lost virulence of TXeta1 was restored when a functionaleta1gene was reintroduced into the strain. Western blot and immunodetection analyses showed that Eta1 is localized to the outer membrane and exposed on the surface ofE. tardaand that recombinant Eta1 (rEta1) was able to interact with flounder lymphocytes. Consistent with these observations, antibody blocking of Eta1 inhibitedE. tardainfection at the cellular level. Furthermore, when used as a subunit vaccine, rEta1 induced strong protective immunity in flounder against lethalE. tardachallenge. Taken together, these results indicate that Eta1 is anin vivo-induced antigen that mediates pathogen-host interaction and, as a result, is required for optimal bacterial infection.

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Section: Discussionsupporting

confidence: 49%

Edwardsiella tarda Eta1, an In Vivo -Induced Antigen That Is Involved in Host Infection

Sun

Zheng

et al. 2012

Infect Immun

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“…Shigella Invaplex was initially formulated from a bacterial extract composed of invasion plasmid antigen proteins (Ipa) which are highly conserved among all Shigella serotypes, and LPS. In animals, only serotype-specific protection has been demonstrated, mediated by the LPS component 79 . Invaplex has been shown to be safe and immunogenic following intranasal delivery in volunteers 80, 81 Current studies are underway to optimize formulation and delivery.…”

Section: Animal Modelsmentioning

confidence: 99%

Progress and pitfalls in Shigella vaccine research

Barry

Pasetti

Sztein

et al. 2013

Nat Rev Gastroenterol Hepatol

121

139

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Renewed awareness of the significant morbidity and mortality that Shigella causes among young children in developing countries combined with technological innovations in vaccinology has led to the development of novel vaccine strategies in the past five years. Along with advancement of classical vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced lending promise to the potential for production of safe and effective Shigella vaccines. Herein we review the recent progress in Shigella vaccine development within the framework of persistent obstacles.

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“…From S. pneumoniae proteome, our web server predicted 10 out of 18 known non-cytoplasmic PVCs whereas the software, NERVE, and servers, Vaxign and VaxiJen, predicted only 7, 6 and 3 PVCs, respectively (Additional file 1: Table S1). As compared to other methods, the PVCs predicted exclusively by Jenner-Predict server were STK [47], NanA [23], and PsaA [48] that are having PASTA, BNR, and SBP domains, respectively (Additional file 1: Table S1). Other than 10 reported vaccine candidates from 69 PVCs (Additional file 3: Table X1), our web server predicted 18 ABC-transporters and solute-binding, 6 choline-binding, 4 penicillin-binding, 2 LysM-containing domain, 3 cell wall anchors, etc.…”

Section: Resultsmentioning

confidence: 99%

“…Choline-binding proteins (CBPs) in some bacteria perform adhesin-like function [39]. Functional classes of proteins involved in virulence [26], invasion [23] and colonization [29]; porins [22] and flagellin [28]; and binding proteins of choline [20], penicillin [27], transferrin [25], fibronectin [24] and solute [21] are important in host-pathogen interactions and pathogenesis. Since many proteins from these functional classes provide protective immune responses against microbial infection [19-31], the knowledge of host-pathogen interactions related to bacterial pathogenesis could be used to rationalize and improve vaccine candidate prediction.…”

Section: Introductionmentioning

confidence: 99%

Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

et al. 2013

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BackgroundSubunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein’s adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs.ResultsA web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and Escherichia coli proteomes. The Jenner-Predict server outperformed NERVE, Vaxign and VaxiJen methods. It has sensitivity of 0.774 and 0.711 for Protegen and VaxiJen dataset, respectively while specificity of 0.940 has been obtained for the latter dataset.ConclusionsBetter prediction accuracy of Jenner-Predict web server signifies that domains involved in host-pathogen interactions and pathogenesis are better criteria for prediction of PVCs. The web server has successfully predicted maximum known PVCs belonging to different functional classes. Jenner-Predict server is freely accessible at http://117.211.115.67/vaccine/home.html

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Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a

Cited by 42 publications

References 30 publications

Edwardsiella tarda Eta1, an In Vivo -Induced Antigen That Is Involved in Host Infection

Edwardsiella tarda Eta1, an In Vivo -Induced Antigen That Is Involved in Host Infection

Progress and pitfalls in Shigella vaccine research

Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

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