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

Hajialibeigi, Abolfazl; Amani, Jafar; Gargari, Seyed Latif Mousavi

doi:10.1007/s00253-020-11054-4

Cited by 16 publications

(8 citation statements)

References 77 publications

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“…This method has been used to identify novel Shigella protein antigens that can induce serotype-independent protection. One such antigen, FimG, a type 1 fimbrial protein, was discovered and became a new efficacious vaccine candidate [77]. Scanning of the S. flexneri 2a proteome in this study revealed seven outer membrane or extracellular proteins that were conserved among various Shigella serotypes but did not have homology with human proteins.…”

Section: Reverse Vaccinologymentioning

confidence: 79%

Recent Progress in Shigella and Burkholderia pseudomallei Vaccines

et al. 2021

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Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of vaccines against intracellular bacterial pathogens. Therefore, new lessons could be learned from different vaccines developed against unrelated intracellular pathogens. Bacillary dysentery and melioidosis are important causes of morbidity and mortality in developing nations, which are caused by the intracellular bacteria Shigella and Burkholderia pseudomallei, respectively. Although the mechanisms of bacterial infection, dissemination, and route of infection do not provide clues about the commonalities of the pathogenic infectious processes of these bacteria, a wide variety of vaccine platforms recently evaluated suggest that in addition to the stimulation of antibodies, identifying protective antigens and inducing T cell responses are some additional required elements to induce effective protection. In this review, we perform a comparative evaluation of recent candidate vaccines used to combat these two infectious agents, emphasizing the common strategies that can help investigators advance effective and protective vaccines to clinical trials.

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Section: Reverse Vaccinologymentioning

confidence: 79%

Recent Progress in Shigella and Burkholderia pseudomallei Vaccines

et al. 2021

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“…In recent years, numerous advancements in in silico tools and algorithms, statistical methods and enormous growth of numerous databases have expanded the sequence-based methodologies in vaccine research and development (Hajialibeigi et al 2021 ). Therefore, in this study, a recombinant chimeric triple antigen toxoid r-HAB was designed, developed and found to be highly immunogenic molecule able to induce strong immune response against the native toxins.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics analysis and evaluation of recombinant chimeric triple antigen toxoid (r-HAB) against Staphylococcus aureus toxaemia in mouse model

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Reddy

et al. 2021

Appl Microbiol Biotechnol

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Staphylococcus aureus is a serious pathogen unleashing its virulence through several classes of exotoxins such as hemolysins and enterotoxins. In this study, we designed a novel multi-antigen subunit vaccine which can induce innate, humoral and cellular immune responses. Alpha hemolysin, enterotoxins A and B were selected as protective antigens for combining into a triple antigen chimeric protein (HAB). Immunoinformatics analysis predicted HAB protein as a suitable vaccine candidate for inducing both humoral and cellular immune responses. Tertiary structure of the HAB protein was predicted and validated through computational approaches. Docking studies were performed between the HAB protein and mice TLR2 receptor. Furthermore, we constructed and generated recombinant HAB (r-HAB) protein in E. coli and studied its toxicity, immunogenicity and protective efficacy in a mouse model. Triple antigen chimeric protein (r-HAB) was found to be highly immunogenic in mouse as the anti-r-HAB hyperimmune serum was strongly reactive to all three native exotoxins on Western blot. In vitro toxin neutralization assay using anti-r-HAB antibodies demonstrated > 75% neutralization of toxins on RAW 264.7 cell line. Active immunization with r-HAB toxoid gave ~ 83% protection against 2 × lethal dosage of secreted exotoxins. The protection was mediated by induction of strong antibody responses that neutralized the toxins. Passive immunization with anti-r-HAB antibodies gave ~ 50% protection from lethal challenge. In conclusion, in vitro and in vivo testing of r-HAB found the molecule to be nontoxic, highly immunogenic and induced excellent protection towards native toxins in actively immunized and partial protection to passively immunized mice groups. Key points • HAB protein was computationally designed to induce humoral and cellular responses. • r-HAB protein was found to be nontoxic, immunogenic and protective in mouse model. • r-HAB conferred protection against lethal challenge in active and passive immunization.

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“…A consensus-based technique was applied for epitopes prediction with binding potency to MHC class-II through the IEBD-AR server ( Hajialibeigi et al, 2021 ). In order to shortlist MHC-II epitopes, a cut-off value of 0.2 peptide rank and an IC 50 of 100 nM for top binders were determined against the worldwide human population's 95 percent HLA variability, i.e., DRB1*0401, DRB1*0701, DRB301:01, DRB1*1301, DRB1*0101, DRB1*0301, DRB1*0801, DRB1*1101, HLA-DRB401:01, DRB1*1501 ( Solanki and Tiwari, 2018 ).…”

Section: Methodsmentioning

confidence: 99%