<i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to th...

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Main Authors: Valentina A. Feodorova, Anna M. Lyapina, Maria A. Khizhnyakova, Sergey S. Zaitsev, Yury V. Saltykov, Vladimir L. Motin
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/4/698
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author Valentina A. Feodorova
Anna M. Lyapina
Maria A. Khizhnyakova
Sergey S. Zaitsev
Yury V. Saltykov
Vladimir L. Motin
author_facet Valentina A. Feodorova
Anna M. Lyapina
Maria A. Khizhnyakova
Sergey S. Zaitsev
Yury V. Saltykov
Vladimir L. Motin
author_sort Valentina A. Feodorova
collection DOAJ
description The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major <i>Yersinia pestis</i> protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated <i>Y. pestis</i> strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.
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spelling doaj.art-1ee10424c0614224a1815be277b85e182023-11-20T21:35:40ZengMDPI AGVaccines2076-393X2020-11-018469810.3390/vaccines8040698<i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological ApproachesValentina A. Feodorova0Anna M. Lyapina1Maria A. Khizhnyakova2Sergey S. Zaitsev3Yury V. Saltykov4Vladimir L. Motin5Laboratory for Molecular Biology and NanoBiotechnology, Federal Research Center for Virology and Microbiology, Branch in Saratov, 410028 Saratov, RussiaLaboratory for Molecular Biology and NanoBiotechnology, Federal Research Center for Virology and Microbiology, Branch in Saratov, 410028 Saratov, RussiaLaboratory for Molecular Biology and NanoBiotechnology, Federal Research Center for Virology and Microbiology, Branch in Saratov, 410028 Saratov, RussiaLaboratory for Molecular Biology and NanoBiotechnology, Federal Research Center for Virology and Microbiology, Branch in Saratov, 410028 Saratov, RussiaLaboratory for Molecular Biology and NanoBiotechnology, Federal Research Center for Virology and Microbiology, Branch in Saratov, 410028 Saratov, RussiaDepartment of Pathology, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAThe recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major <i>Yersinia pestis</i> protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated <i>Y. pestis</i> strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.https://www.mdpi.com/2076-393X/8/4/698<i>Yersinia pestis</i>plaguevaccineimmune responseepitope mappingpeptide
spellingShingle Valentina A. Feodorova
Anna M. Lyapina
Maria A. Khizhnyakova
Sergey S. Zaitsev
Yury V. Saltykov
Vladimir L. Motin
<i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
Vaccines
<i>Yersinia pestis</i>
plague
vaccine
immune response
epitope mapping
peptide
title <i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
title_full <i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
title_fullStr <i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
title_full_unstemmed <i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
title_short <i>Yersinia pestis</i> Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches
title_sort i yersinia pestis i antigen f1 but not lcrv induced humoral and cellular immune responses in humans immunized with live plague vaccine comparison of immunoinformatic and immunological approaches
topic <i>Yersinia pestis</i>
plague
vaccine
immune response
epitope mapping
peptide
url https://www.mdpi.com/2076-393X/8/4/698
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