دورية أكاديمية
أعرض في EDS

Challenges for the development of a universal vaccine against leptospirosis revealed by the evaluation of 22 vaccine candidates.

التفاصيل البيبلوغرافية
العنوان: Challenges for the development of a universal vaccine against leptospirosis revealed by the evaluation of 22 vaccine candidates.
المؤلفون: Maia MAC; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Bettin EB; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Barbosa LN; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., de Oliveira NR; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Bunde TT; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Pedra ACK; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Rosa GA; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., da Rosa EEB; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Seixas Neto ACP; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., Grassmann AA; Department of Medicine, University of Connecticut Health, Farmington, CT, United States., McFadden J; School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom., Dellagostin OA; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil., McBride AJA; Biotechnology Unit, Technological Development Centre, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.; School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
المصدر: Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2022 Oct 07; Vol. 12, pp. 940966. Date of Electronic Publication: 2022 Oct 07 (Print Publication: 2022).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Media SA
مواضيع طبية MeSH: Leptospirosis*/prevention & control , Leptospira*, Cricetinae ; Humans ; Mice ; Animals ; Aluminum Hydroxide ; Reproducibility of Results ; Bacterial Vaccines ; Antigens, Bacterial/genetics ; Recombinant Proteins ; Escherichia coli ; Immunoglobulin G ; Epitopes
مستخلص: Leptospirosis is a neglected disease of man and animals that affects nearly half a million people annually and causes considerable economic losses. Current human vaccines are inactivated whole-cell preparations (bacterins) of Leptospira spp. that provide strong homologous protection yet fail to induce a cross-protective immune response. Yearly boosters are required, and serious side-effects are frequently reported so the vaccine is licensed for use in humans in only a handful of countries. Novel universal vaccines require identification of conserved surface-exposed epitopes of leptospiral antigens. Outer membrane β-barrel proteins (βb-OMPs) meet these requirements and have been successfully used as vaccines for other diseases. We report the evaluation of 22 constructs containing protein fragments from 33 leptospiral βb-OMPs, previously identified by reverse and structural vaccinology and cell-surface immunoprecipitation. Three-dimensional structures for each leptospiral βb-OMP were predicted by I-TASSER. The surface-exposed epitopes were predicted using NetMHCII 2.2 and BepiPred 2.0. Recombinant constructs containing regions from one or more βb-OMPs were cloned and expressed in Escherichia coli . IMAC-purified recombinant proteins were adsorbed to an aluminium hydroxide adjuvant to produce the vaccine formulations. Hamsters (4-6 weeks old) were vaccinated with 2 doses containing 50 - 125 μg of recombinant protein, with a 14-day interval between doses. Immunoprotection was evaluated in the hamster model of leptospirosis against a homologous challenge (10 - 20× ED 50 ) with L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni strain Fiocruz L1-130. Of the vaccine formulations, 20/22 were immunogenic and induced significant humoral immune responses (IgG) prior to challenge. Four constructs induced significant protection (100%, P < 0.001) and sterilizing immunity in two independent experiments, however, this was not reproducible in subsequent evaluations (0 - 33.3% protection, P > 0.05). The lack of reproducibility seen in these challenge experiments and in other reports in the literature, together with the lack of immune correlates and commercially available reagents to characterize the immune response, suggest that the hamster may not be the ideal model for evaluation of leptospirosis vaccines and highlight the need for evaluation of alternative models, such as the mouse.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Maia, Bettin, Barbosa, de Oliveira, Bunde, Pedra, Rosa, da Rosa, Seixas Neto, Grassmann, McFadden, Dellagostin and McBride.)
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فهرسة مساهمة: Keywords: Leptospira interrogans; animal model; cell-surface immunoprecipitation; outer membrane proteins; reverse and structural vaccinology
المشرفين على المادة: 5QB0T2IUN0 (Aluminum Hydroxide)
0 (Bacterial Vaccines)
0 (Antigens, Bacterial)
0 (Recombinant Proteins)
0 (Immunoglobulin G)
0 (Epitopes)
تواريخ الأحداث: Date Created: 20221024 Date Completed: 20221025 Latest Revision: 20221222
رمز التحديث: 20221222
مُعرف محوري في PubMed: PMC9586249
DOI: 10.3389/fcimb.2022.940966
PMID: 36275031
قاعدة البيانات: MEDLINE
الوصف
تدمد:2235-2988
DOI:10.3389/fcimb.2022.940966