Dataset Information

Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery.

ABSTRACT: Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group B meningococcus (MenB) vaccine in early 1990's, several software programs have been developed implementing different flavors of the first RV protocol. However, there has been no comprehensive review to date on these different RV tools. We have compared six of these applications designed for bacterial vaccines (NERVE, Vaxign, VaxiJen, Jenner-predict, Bowman-Heinson, and VacSol) against a set of 11 pathogens for which a curated list of known bacterial protective antigens (BPAs) was available. We present results on: (1) the comparison of criteria and programs used for the selection of PVCs (2) computational runtime and (3) performances in terms of fraction of proteome identified as PVC, fraction and enrichment of BPA identified in the set of PVCs. This review demonstrates that none of the programs was able to recall 100% of the tested set of BPAs and that the output lists of proteins are in poor agreement suggesting in the process of prioritize vaccine candidates not to rely on a single RV tool response. Singularly the best balance in terms of fraction of a proteome predicted as good candidate and recall of BPAs has been observed by the machine-learning approach proposed by Bowman (1) and enhanced by Heinson (2). Even though more performing than the other approaches it shows the disadvantage of limited accessibility to non-experts users and strong dependence between results and a-priori training dataset composition. In conclusion we believe that to significantly enhance the performances of next RV methods further studies should focus on the enhancement of accuracy of the existing protein annotation tools and should leverage on the assets of machine-learning techniques applied to biological datasets expanded also through the incorporation and curation of bacterial proteins characterized by negative experimental results.

SUBMITTER: Dalsass M

PROVIDER: S-EPMC6382693 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery.

Dalsass Mattia M Brozzi Alessandro A Medini Duccio D Rappuoli Rino R

Frontiers in immunology 20190214

Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group B <i>meningococcus</i> (MenB) vaccine in early 1990's, several software programs have been developed implementing different flavors of the first RV protocol. However, there has been no comprehensive review to date on these different RV tools. We have compared six of these applications design ...[more]

PMID: 30837982

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Project description:Leptospira spp. are diderm (two membranes) bacteria that infect mammals causing leptospirosis, a public health problem with global implications. Thousands of people die every year due to leptospirosis, especially in developing countries with tropical climates. Prophylaxis is difficult due to multiple factors, including the large number of asymptomatic hosts that transmit the bacteria, poor sanitation, increasing numbers of slum dwellers, and the lack of an effective vaccine. Several leptospiral recombinant antigens were evaluated as a replacement for the inactivated (bacterin) vaccine; however, success has been limited. A prospective vaccine candidate is likely to be a surface-related protein that can stimulate the host immune response to clear leptospires from blood and organs. In this study, a comprehensive bioinformatics approach based on reverse and structural vaccinology was applied toward the discovery of novel leptospiral vaccine candidates. The Leptospira interrogans serovar Copenhageni strain L1-130 genome was mined in silico for the enhanced identification of conserved β-barrel (βb) transmembrane proteins and outer membrane (OM) lipoproteins. Orthologs of the prospective vaccine candidates were screened in the genomes of 20 additional Leptospira spp. Three-dimensional structural models, with a high degree of confidence, were created for each of the surface-exposed proteins. Major histocompatibility complex II (MHC-II) epitopes were identified, and their locations were mapped on the structural models. A total of 18 βb transmembrane proteins and 8 OM lipoproteins were identified. These proteins were conserved among the pathogenic Leptospira spp. and were predicted to have epitopes for several variants of MHC-II receptors. A structural and functional analysis of the sequence of these surface proteins demonstrated that most βb transmembrane proteins seem to be TonB-dependent receptors associated with transportation. Other proteins identified included, e.g., TolC efflux pump proteins, a BamA-like OM component of the βb transmembrane protein assembly machinery, and the LptD-like LPS assembly protein. The structural mapping of the immunodominant epitopes identified the location of conserved, surface-exposed, immunogenic regions for each vaccine candidate. The proteins identified in this study are currently being evaluated for experimental evidence for their involvement in virulence, disease pathogenesis, and physiology, in addition to vaccine development.

Project description:BackgroundThe horn fly, Haematobia irritans irritans, causes significant production losses to the cattle industry. Horn fly control relies on insecticides; however, alternative control methods such as vaccines are needed due to the fly's capacity to quickly develop resistance to insecticides, and the pressure for eco-friendly options.MethodsWe used a reverse vaccinology approach comprising three vaccine prediction and 11 annotation tools to evaluate and rank 79,542 translated open reading frames (ORFs) from the horn fly's transcriptome, and selected 10 transcript ORFs as vaccine candidates for expression in Pichia pastoris. The expression of the 10 selected transcripts and the proteins that they encoded were investigated in adult flies by reverse transcription polymerase chain reaction (RT-PCR) and mass spectrometry, respectively. Then, we evaluated the immunogenicity of a vaccine candidate in an immunization trial and the antigen's effects on horn fly mortality and fecundity in an in vitro feeding assay.ResultsSix of the ten vaccine candidate antigens were successfully expressed in P. pastoris. RT-PCR confirmed the expression of all six ORFs in adult fly RNA. One of the vaccine candidate antigens, BI-HS009, was expressed in sufficient quantity for immunogenicity and efficacy trials. The IgG titers of animals vaccinated with BI-HS009 plus adjuvant were significantly higher than those of animals vaccinated with buffer plus adjuvant only from days 42 to 112, with a peak on day 56. Progeny of horn flies feeding upon blood from animals vaccinated with BI-HS009 plus adjuvant collected on day 56 had 63% lower pupariation rate and 57% lower adult emergence than the control group (ANOVA: F (1, 6) = 8.221, P = 0.028 and F (1, 6) = 8.299, P = 0.028, respectively).ConclusionsThe reverse vaccinology approach streamlined the discovery process by prioritizing possible vaccine antigen candidates. Through a thoughtful process of selection and in vivo and in vitro evaluations, we were able to identify a promising antigen for an anti-horn fly vaccine.

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Dataset Information

Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery.

Publications

Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery.

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