Humoral and cellular immune responses to Yersinia pestis Pla antigen in humans immunized with live plague vaccine

Abstract

BackgroundTo 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.Methodology/Principal findingsPBMCs 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.Conclusions/SignificanceThe 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.

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

“…The IL-17 response was reduced in both strains of mice that received acetaminophen, which may predispose them to more protracted pathogen clearance, especially if this results in reduced granulopoiesis [102]. A significant IL-17 response was also documented when looking at samples collected from humans receiving a live plague vaccine [46]. In C57BL/6 mice, reduced granulopoiesis and monopoiesis, due to acetaminophen, may also be further impaired with reduced levels of G-CSF and M-CSF leading to acquired cytopenia [103].…”

“…From a biodefense perspective, pneumonic plague remains a scenario of concern due to person-to-person transmission and a low infectious dose [45]. Plague vaccines, including live vaccine strategies at various stages of development, are being investigated [46][47][48][49]. We hypothesized that antipyretic analgesics, specifically acetaminophen and meloxicam, would alter the immune response in mice if used during vaccination with a live bacterial vaccine.…”

New Promising Targets for Synthetic Omptin-Based Peptide Vaccine against Gram-Negative Pathogens

“…A detailed protocol of this study has been published, describing the study design, study population, and methods including consenting procedures, assessment of immune-serological B-cells, and T-cells immune responses of human donors vaccinated with LPV as well as non-vaccinated donors [28,29,30]. Overall, sera from vaccinated donors ( n = 18) who received multiple annual immunizations with LPV and unvaccinated healthy individuals ( n = 6) who had never been in contact with either Y. pestis or its antigens participated in the study.…”

“…A library of 61 overlapping synthetic peptides, each 15 amino acid residues in length (offset by 5 residues at a time) was made by GenScript, Piscataway, NJ, USA as described recently [30].…”

“…We used the prototypical omptin as a model target antigen—a His-tagged recombinant Pla (pro-omptin) purified under denaturing conditions [27]. We screened a set of sera from human volunteers who were multiply vaccinated with live plague vaccine (LPV) to identify Pla-specific epitopes [28,29,30]. To reveal common anti-omptin epitopes, we also used a panel of sera from unvaccinated donors with detectable level of antibodies to Pla who had possible history of prior enteric bacterial diseases.…”