[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Humoral and cellular immune responses to Yersinia pestis Pla antigen in humans immunized with live plague vaccine
Valentina A. Feodorova , Anna M. Lyapina, Maria A. Khizhnyakova, Sergey S. Zaitsev, Lidiya V. Sayapina, Tatiana E. Arseneva, Alexey L. Trukhachev, Svetlana A. Lebedeva, Maxim V. Telepnev, Onega V. Ulianova, Elena P. Lyapina, Sergey S. Ulyanov, Vladimir L. Motin
Published: June 11, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006511
To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis.
PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting. The analysis of antibody response was complicated with a strong reactivity of Pla with normal human sera. The linear Pla B-cell epitopes were mapped using a library of 15-mer overlapping peptides. Twelve peptides that reacted specifically with sera of vaccinated donors were found together with a major cross-reacting peptide IPNISPDSFTVAAST located at the N-terminus. PBMCs were stimulated with recombinant Pla followed by proliferative analysis and cytokine profiling. The T-cell recall response was pronounced in vaccinees less than a year post-immunization, and became Th17-polarized over time after many rounds of vaccination.
The Pla protein can serve as a biomarker of successful vaccination with LPV. The diagnostic use of Pla will require elimination of cross-reactive parts of the antigen.
Yersinia pestis, the causative agent of plague, has been recognized as one of the most devastating pathogen experienced by mankind. It remains endemic in many parts of the world, and is considered emerging pathogen. A live attenuated Y. pestis strain EV line NIIEG has been used for decades in the former Soviet Union for human vaccination and has proven effective against all forms of plague. We began characterizing the Y. pestis-specific antibody and T cell-mediated immune responses in people immunized with live plague vaccine. The long term goal of our research is to understand the protective mechanisms underlying immunity to plague in humans and to discover novel protective antigens for their incorporation into a subunit vaccine. Here, we describe our study on immune responses in vaccinees to one of the essential virulence factors of Y. pestis, namely Pla antigen. The results of the study shed light on the development of the optimal markers to assess the correlation with vaccine-induced protection.
Citation: Feodorova VA, Lyapina AM, Khizhnyakova MA, Zaitsev SS, Sayapina LV, Arseneva TE, et al. (2018) Humoral and cellular immune responses to Yersinia pestisPla antigen in humans immunized with live plague vaccine. PLoS Negl Trop Dis 12(6): e0006511. https://doi.org/10.1371/journal.pntd.0006511
Editor: David Joseph Diemert, George Washington University School of Medicine and Health Sciences, UNITED STATES
Received: December 30, 2017; Accepted: May 8, 2018; Published: June 11, 2018
Copyright: © 2018 Feodorova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: Plan of Fundamental Research of Russian Academies of Sciences, # 0755-2015-0004; Russian Foundation for Basic Research, Grant No. 2616-34-00051. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Keywords: Yersinia Pestis; Plague; Vaccines.