Plague Vaccine Research Articles

Direct Detection of Antibodies to <i>Yersinia pestis</i> Using Glass Microstructural Waveguides as an Express Method for Assessing Seroconversion in Individuals Vaccinated against Plague

Relevance. As part of ensuring sanitary and epidemiological well­-being, in the territory of natural plague foci of the Russian Federation, according to epidemiological indications, the population is vaccinated against this infection. The lack of a unified scheme for evaluating the effectiveness of vaccination dictates the need to develop universal express methods that allow screening studies of anti­-plague immunity, including in the field.Aims. To evaluate the effectiveness of the express method for the direct detection of antibodies to Yersinia pestis in biological material using microstructural glass waveguides with a hollow core (MGW HC) as immunosensors in studying the dynamics of seroconversion in people vaccinated with the plague live people.Materials and methods. In the study, blood serum samples were taken from 30 individuals vaccinated according to epidemic indications with the live plague vaccine (PLV) and 30 volunteers who were not vaccinated and did not have a history of contact with the plague agent.Results. An assessment was made of the possibility of using the method of direct detection of antibodies using MGW HC at different time intervals according to the receipt of blood sera in the framework of monitoring vaccinated individuals from among the inhabitants of the Caspian sandy natural plague focus. The presence of specific antibodies to the F1 protein in the blood serum of vaccinated volunteers was revealed both with the help of ELISA and with the use of MGW HC. The speed of the method of direct detection of antibodies (maximum 2 minutes per test), the absence of the need to use species­specific secondary antibodies, enzymes and substrates and additional costs for laborious sample preparation were noted.Conclusions. The method of direct detection of antibodies using glass microstructural waveguides is promising for introduction into the list of express methods for assessing the immunological effectiveness of anti­plague vaccination.

Determination of Conformational and Functional Stability of Potential Plague Vaccine Candidate in Formulation.

Generally, protein-based vaccines are available in liquid form and are highly susceptible to instability under elevated temperature changes including freezing conditions. There is a need to create a convenient formulation of protein/peptides that can be stored at ambient conditions without loss of activity or production of adverse effects. The efficiency of naturally occurring biocompatible polymer dextran in improving the shelf-life and biological activity of a highly thermally unstable plague vaccine candidate protein called Low Calcium Response V antigen (LcrV), which can be stored at room temperature (30 ± 2 °C), has been evaluated. To determine the preferential interactions with molecular-level insight into solvent-protein interactions, analytical techniques such asspectroscopy, particle size distribution, gel electrophoresis, microscopy, and thermal analysis have been performed along with the evaluation of humoral immune response, invivo. The analytical methods demonstrate the structural stability of the LcrV protein by expressing its interaction with the excipients in the formulation. The invivo studies elicited the biological activity of the formulated antigen with a significantly higher humoral immune response (p-value = 0.047) when compared to the native, adjuvanted antigen. We propose dextran as a potential biopolymer with its co-excipient sodium chloride (NaCl) to provide protein compactness, i.e., prevent protein unfolding by molecular crowding or masking mechanism using preferential hydrophobic interaction for up to three weeks at room temperature (30 ± 2 °C).

Analysis of the Features of the Genomic Organization of Plague Microbe Strains Suitable for the Creation of a New Attenuated Vaccine

Relevance. To date, the specific prevention of plague remains the most effective measure to prevent to prevent the deterioration of the epidemiological situation for this especially dangerous infection in the territory of the Russian Federation. The development of new vaccine preparations created on the basis of avirulent strains of Yersinia pestis with specific genetic defects, can play a crucial importance in the issues of plague immunoprophylaxis.Aim. Determination and comparative analysis of the genomic organization of avirulent strains Y. pestis I-1, Y. pestis I-3536 and vaccine strain Y. pestis EV line NIIEG.Materials and methods. The features of the genetic structure of three Y. pestis strains were studied using plasmid screening and whole genome sequencing.Results and discussion. It was found that the Y. pestis I-1 and Y. pestis I-3536 strains, like Y. pestis EV, lack the chromosomal pgm region. Analysis the genome sequence of Y. pestis I-1 showed that this strain is devoid of the plasmid pMT1, while its individual genes were found in the chromosome structure and the unique 340 kb plasmid. It was revealed that the Y. pestis strain I-3536 lost the plasmid pCD1, however, fragments homologous to this plasmid were found in the structure of its genome.Conclusion. The data obtained allow us to recommend Y. pestis I-1 and Y. pestis I-3536 as the basis for the development of a modern live attenuated plague vaccine.

Activation of T-helper in vitro under the Influence of Yersinia pestis Antigens in People Vaccinated against the Plague

Relevance. The search for informative markers for assessing the immunological efficacy of a live plague vaccine remains an urgent scientific task. The goal of the studyAims was to make a comparative assessment of the level helper T-cells activation by CD69 and HLA-DR markers, in people, vaccinated against plague, in an in vitro test, using the disintegrated by ultrasonic Y. pestis cells, grown at temperature 28 °C as a specific stimulator.Materials & Methods. A cytofluorimetric analysis of blood samples of 45 individuals vaccinated against the plague was carried out. The dependence of the result of cytological analysis of the two studied cell markers on the immunoregulatory index (IRI) of the vaccinated donor at the time of vaccination was revealed.Results. It was found that for newly vaccinated individuals, the T-helpers were more intensive and prolonged by the early activation marker, while for those revaccinated with the immunoregulatory index, at the time of vaccination more than 1.5, the more intense cellular response was by the late activation marker.Conclusions. Thus, the possibility of quantitative evaluation of the immunological efficacy of vaccination against plague, based on the identification of lymphocyte activation markers when stimulated with a specific antigen, is confirmed.

<i>In silico</i> Research at the Stages of Designing Modern Means for Prevention of Plague (by the Example of Subunit Vaccines)

The purpose of this review was to analyze the findings of domestic and foreign researchers on the development of modern drugs for the specific prevention of plague and to illustrate the possibilities of using bioinformatics analysis at the design stages to create an effective and safe vaccine. Work on the creation of an effective new-generation plague vaccine is hampered by several factors associated primarily with the presence of mechanisms of evasion from the immune system of the macroorganism, as well as a large number of pathogenicity determinants in the plague agent. Due to the development of approaches that are based on in silico studies, there is a progressive development of vaccine technologies oriented primarily to the use of the most important immunogens of the plague microbe (F1 and V antigen). Studies aimed at improving the antigenic properties of F1 and LcrV, as well as work on bioinformatic search and analysis of additional promising components to be included in the composition of subunit vaccines are considered as topical applications of bioinformatics data analysis in developing the tools for enhancing the effectiveness of protection through vaccination with subunit preparations.

The Effect of Cryopreservation on the Survival of Nocardia farcinica and Yersinia pestis vaccine strains.

Pathogenic microorganisms are valuable biological resources, closely related to biosecurity, human health, environmental protection, and renewable energy. It is very important to properly preserve the microbial resources by methods to maintain the purity, viability, and integrity, and to avoid prolonged degradation. The present work aims to explore the cryopreservation technology of Nocardia farcinica (Gram-positive bacteria) and Yersinia pestis vaccine strains (Gram-negative bacteria). The effects of cryoprotectants (CPAs), freezing temperature, and freeze-thaw cycles on the two bacteria in the cryopreservation process were studied. The results showed that the addition of CPAs (glycerol, propylene glycol, sucrose, glucose, l-carnitine, l-proline, and skim milk) significantly enhanced the survival rates of the N. farcinica and Y. pestis vaccine strains. However, high concentrations of CPAs can produce biochemical toxicity in the two pathogens. The utilization of composite CPAs not only reduced the toxicity but also improved the survival rates of samples during cryopreservation. The optimal composite CPA for N. farcinica is 0.292 M sucrose, 0.62 M l-carnitine, and 2.82 M glycerol. The optimal composite CPA for Y. pestis is 0.62 M l-carnitine, 8.46 M glycerin, and 0.292 M sucrose. The results showed that the quality of the strains stored at -80°C and -196°C was better. For the case of freeze-thaw cycles, the two pathogens have different degrees of reduction, and the survival rate of Y. pestis decreased more than that of N. farcinica. The uniform distribution of bacteria in CPAs can form uniform nucleation sites in the solution system, which is beneficial to the cryopreservation of strains, as can be seen from the experimental results from a differential scanning calorimeter. This study may provide a reference for better preservation of precious natural biological resources of pathogenic microorganisms.

CD4+ T-Cell Epitope Prediction by Combined Analysis of Antigen Conformational Flexibility and Peptide-MHCII Binding Affinity.

Antigen processing in the class II MHC pathway depends on conventional proteolytic enzymes, potentially acting on antigens in native-like conformational states. CD4+ epitope dominance arises from a competition among antigen folding, proteolysis, and MHCII binding. Protease-sensitive sites, linear antibody epitopes, and CD4+ T-cell epitopes were mapped in plague vaccine candidate F1-V to evaluate the various contributions to CD4+ epitope dominance. Using X-ray crystal structures, antigen processing likelihood (APL) predicts CD4+ epitopes with significant accuracy for F1-V without considering peptide-MHCII binding affinity. We also show that APL achieves excellent performance over two benchmark antigen sets. The profiles of conformational flexibility derived from the X-ray crystal structures of the F1-V proteins, Caf1 and LcrV, were similar to the biochemical profiles of linear antibody epitope reactivity and protease sensitivity, suggesting that the role of structure in proteolysis was captured by the analysis of the crystal structures. The patterns of CD4+ T-cell epitope dominance in C57BL/6, CBA, and BALB/c mice were compared to epitope predictions based on APL, MHCII binding, or both. For a sample of 13 diverse antigens, the accuracy of epitope prediction by the combination of APL and I-Ab-MHCII-peptide affinity reached 36%. When MHCII allele specificity was also diverse, such as in human immunity, prediction of dominant epitopes by APL alone reached 42% when using a stringent scoring threshold. Because dominant CD4+ epitopes tend to occur in conformationally stable antigen domains, crystal structures typically are available for analysis by APL, and thus, the requirement for a crystal structure is not a severe limitation.

SA19 A Systematic Review of the Efficacy, Safety and Immunogenicity of Plague Vaccines

SA19 A Systematic Review of the Efficacy, Safety and Immunogenicity of Plague Vaccines

Identifying correlates of protection from <i>Yersinia pestis</i> on a mouse model and assessing an opportunity for their use as markers of human vaccination efficiency

In case no assessment of changes in incidence rate can be used as an indicator for effectiveness of applied live plague vaccine, it is really necessary to search for other, particularly immunological correlates for vaccine-based protection. The aim of this study was to reveal immunological correlates for plague protection in mice immunized with Yersinia pestis EV NIIEG, and assess dynamics changes in select markers of plague vaccinated subjects. BALB/c mice were immunized with Y. pestis EV at dose of 2 102, 1 103, 5 103, 2.5 104 CFU, and on day 21 they were challenged with Y. pestis 231 at a dose of 400 LD50. Immunogenicity was calculated by the Kerber method and ImD50 was determined. Volunteers 20 subjects who were first vaccinated with live plague vaccine and 20 subjects who were not vaccinated against the plague. Blood cytokine production was measured on the LAZURIT analyzer (Dynex Technologies, USA) in mouse groups before Y. pestis 231 infection on day 14 as well as 21 days after vaccination, in humans before vaccination, 1, 6 and 12 months after vaccination. The immunized mice showed a significant increase (by 2.2 times) in the induced production of IFN and a moderate increase in the concentration of TNF, IL-10 and IL-17A on day 14 of disease. A high correlation was found between the survival rate of animals and the level of antigen-/mitogen-induced IFN production (r = 0.94, p = 0.039), both on day 14 and 21, as well as a noticeable relationship with the level of produced IL-10 and IL-17A on day 14. One month after vaccination volunteers had significantly increase by month 6 (p 0.05) levels of IFN, TNF, IL-10, IL-17A, although only for IFN and IL-17A, the persistence of induced production was noted at a fairly high level for up to a year. Thus, IFN and IL-17A can be considered as possible informative correlates of mouse protection against Y. pestis on days 14 and 21, considering the increase in the induced production of these cytokines as adequate markers of the protective efficacy of immunization, and assessing dynamics in these parameters of volunteers vaccinated with the plague live vaccine, the increase in the levels of IFN and IL-17A can be considered as a favorable prognostic marker of the immunological efficacy of the vaccine in the period from the month 6 to 12 of observation.

Remodeling Yersinia pseudotuberculosis to generate a highly immunogenic outer membrane vesicle vaccine against pneumonic plague

SignificanceYersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. This plague bacillus has been used as a biological weapon during human history and is currently one of the deadliest biological threats. Currently, no licensed plague vaccines are available in the Western world. Since an array of immunogens are enclosed in outer membrane vesicles (OMVs), immune responses elicited by OMVs against a diverse range of antigens may reduce the likelihood of antigen circumvention. Therefore, self-adjuvanting OMVs from a remodeled Yersinia pseudotuberculosis strain as a type of plague vaccine could diversify prophylactic choices and solve current vaccine limitations.

Predictors of Survival after Vaccination in a Pneumonic Plague Model.

Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. Results: Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. Conclusions: These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy.

Prevalence and risk factors of Avian Influenza Viruses among household ducks in Chattogram, Bangladesh.

Avian influenza viruses (AIV) increase commercial and backyard poultry mortality and morbidity, reduces egg production, and elevates public health risk. Household ducks propagate and transmit HPAI and LPAI viruses between domesticated and wild birds in Southeast Asian countries, including Bangladesh. This study was conducted to identify epidemiological factors associated with AIV infection among household ducks at Chattogram, Bangladesh. We randomly selected and collected blood and oropharyngeal swab samples from 281 households ducks. We evaluated the serum for AIV antibody using cELISA and tested for H5 and H9 subtypes using the HI test. We tested the swabs with real-time reverse transcriptase PCR (rRT-PCR) for M gene, and H5, H9 subtypes. In the duck populations, the household level AIV sero-prevalence was 57.7% (95% CI: 51.6-63.3) and RNA prevalence was 2.4% (95% CI: 1.0-5.0). H5 and H9 subtype sero-prevalence was 31.5% (95% CI: 22.2-42.0) and 23.9% (95% CI: 15.6-33.9). H5 and H9 subtype RNA prevalence were 0% (95% CI: 0.0-1.3) and 2.4% (95% CI: 1.0-5.0). We determined household-level OR (Odds Ratios) for the "combined (mixed materials-mud and concrete or metallic)" category was 2.2 (95% CI: 1.1-4.2) compared with "wooden/bamboo" category (p = 0.02); 2.8 (95% CI: 1.2-6.6) in households with duck plague vaccine coverage compared with no coverage (p = 0.01); and 2.4 (95% CI: 0.6-9.7) in households that threw dead birds in bushes and the roadside compared with households that buried or threw dead birds in garbage pits (p = 0.21). M gene phylogenetic analysis compared M gene sequences to previously reported Bangladeshi H9N2 isolates. The evidence presented here shows AIV circulation in the Chattogram, Bangladesh study areas. AIV reduction can be achieved through farmer education of proper farm management practices.

Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection against Yersinia pestis Infection.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. A similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with maximally hydrolyzed peptidoglycan had a greater protectivity compared to BGs with a preserved peptidoglycan skeleton.

Efficiency of human plague vaccination in tuvinian natural plague focus. Message 2: dynamics of immune status indicators after revaccination

Relevance. In Russia, the live plague vaccine (LPV) is used for specific prophylaxis of plague. Immunological monitoring of humans vaccinated by LPV in order to search for informative diagnostic markers, as well as to improve the tactics of epidemiological surveillance of plague enzootic territories is an urgent area of research.The aim is to assess the parameters of cellular and humoral immunity in humans revaccinated by LPV who permanently reside on territory of the Tuvinian natural plague focus.Materials and methods. The study involved 76 volunteers from the Republic of Tuva, revaccinated by LPV. Blood sampling was performed before vaccination and 1, 3, and 6 months after revaccination. The study included the determination of cytokine production (IFN-γ, IL-4, TNF-α), specific antibodies, immunoglobulins (IgM, IgG, IgA and IgE) and lymphocyte subpopulation composition (CD3, CD4, CD8, CD16, CD19, immunoregulatory index).Results. A decrease in IgG and IgM and an increase in IgA were found after vaccination with LPV and their increase after revaccination. Correlation relationships were revealed between immunoglobulins, B cells and IL-4. Revaccination leads to an increase seroconversion. The activation of humoral immunity in humans vaccinated against plague is also evidenced by dynamics of changes in the subpopulation composition: an increase in B-lymphocytes and natural killer cells, a decrease in T-helpers and immunoregulatory index, and cellular immunity stimulation is an increase in spontaneous and induced production of pro- and anti-inflammatory cytokines.Conclusion. It has been shown that LPV is capable of causing the body’s immune restructuring and activating the cellular and humoral mechanisms of immunological protection. For a complete understanding of the development and preservation of antiplague immunity, it is necessary to continue the annual immunological monitoring of the population living on the territory of the Tuvinian natural plague focus, using additional modern research methods.

Oral Sylvatic Plague Vaccine Does Not Adequately Protect Prairie Dogs (Cynomys spp.) for Endangered Black-Footed Ferret (Mustela nigripes) Conservation.

The plague bacterium Yersinia pestis is lethal to endangered black-footed ferrets (Mustela nigripes, BFF) and the prairie dogs (Cynomys spp., PD) on which they depend for habitat and prey. We assessed the effectiveness of an oral sylvatic plague vaccine delivered in baits to black-tailed PD (Cynomys ludovicianus, BTPD) from 2013 to 2017 on the Charles M. Russell National Wildlife Refuge (CMR) in northcentral Montana. We permanently marked BTPD on four paired vaccine (N = 1,349 individuals) and placebo plots (N = 926; 7,027 total captures). We analyzed capture–recapture data under a Cormack–Jolly–Seber model to estimate annual apparent survival. Overall, survival averaged 0.05 lower on vaccine plots than on paired placebo plots. Immediately before noticeable die-offs and detecting plague on pairs CMR1 and CMR2, 89% of BTPD sampled on vaccine plots had consumed at least one bait and the immune systems of 40% were likely boosted by consuming baits over multiple years. Survival to the following year was 0.16 and 0.05 on the vaccine plots and 0.19 and 0.06 on the placebo plots for pairs CMR1 and CMR2, respectively. These rates were markedly lower than 0.63, the overall average estimate on those same plots during the previous 3 years. PD populations subjected to such large die-offs would not be expected to sustain a BFF population. An overriding limitation to achieving sufficient protection rests with vaccine delivery constraints. Late summer/fall bait distribution results in the highest bait uptake rates. However, the PD birth pulse each spring can double the size of populations in most years, greatly reducing the proportion of vaccinates in populations and diminishing potential herd immunity benefits. In addition to nonvaccinated juveniles and PD that do not consume bait, incomplete vaccine protection and time required for immunity to develop leaves a large majority of PD populations vulnerable to plague for 6–7 months or more each year.

Impact of Toll-Like Receptor-Specific Agonists on the Host Immune Response to the Yersinia pestis Plague rF1V Vaccine.

Relatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein. Accordingly, questions remain surrounding its efficacy against infection with non-encapsulated (F1-negative) strains. In an attempt to further optimize the F1-V elicited immune response and address efficacy concerns, we examined the inclusion of multiple toll-like receptor agonists into vaccine regimens. We examined the resulting immune responses and also any protection afforded to mice that were exposed to aerosolized Yersinia pestis. Our data demonstrate that it is possible to further augment the F1-V vaccine strategy in order to optimize and augment vaccine efficacy.

Comparative Analysis of the Immunogenic Activity of the Plague Vaccine Depending on the Growing Medium

The aim was to carry out a comparative analysis of the immunogenic activity of the live plague vaccine obtained on various nutrient media.Materials and methods. The subject of the study was the blood of outbred white mice immunized with a series of live plague vaccine based on Yersinia pestis EV NIIEG strain, produced using experimental and regulated nutrient media. The immunogenic activity of vaccines was studied through flow cytometry. The intensity of antigen-reactivity of lymphocytes was determined in cell tests in vitro, analyzing the early activation marker CD25+ . For the specific activation of lymphocytes, a complex of water-soluble antigens of the plague microbe was used. To identify the interdependence between the presence of protective anti-plague immunity and the level of CD 25+ expression intensity, the ED50 of the series under study was determined by the standard method.Results and discussion. A comparative analysis of the immunogenic activity of the live plague vaccine obtained on the experimental nutrient medium with the vaccine produced on Hottinger’s agar has been performed. When animals were immunized with doses of 4·103 , 2·104 and 1·105 live microbial cells (regulated doses), the highest level of expression of CD25 marker by lymphocytes was on the day 14, with a subsequent decrease on the day 21 after vaccination. When determining immunogenicity using the conventional method, a high degree of direct correlation between the number of surviving animals and an increase in the level of lymphocytes expressing markers of early activation has been established. Comparison has revealed the general pattern: when the lowest immunizing dose (8·102 ) was administered, activation of early immunity markers was not observed. In case of immunization with higher doses on days 7, 14 and 21, a proportional increase in the number of CD25-positive lymphocytes after stimulation with a specific antigen under in vitro conditions is detected in the blood of biomodels.

Information support for monitoring post-vaccination immunity against plague

Relevance. The widespread use of information technologies, both when creating a database based on the results of immunological monitoring of persons vaccinated with the live plague vaccine, and for predicting the effectiveness of measures for specific prevention of plague in a specific territory, is aimed at ensuring epidemiological surveillance of plague in the territories of natural foci of infection. The aim of the work was to analyze the application of the created replenished database, which allows accumulating, archiving and systematizing the results of immunological monitoring of persons vaccinated against plague for informational support of sanitary and epidemiological surveillance of plague in the territories of natural foci of infection.Materials and methods. The database included the results of a prospective cohort observational study. The database was created on the Microsoft Access 8.0 platform, an interactive software development environment for Visual Basic 6.0 with VB (Visual Basic) and / or SQL (structured query language) queries. To store the data, TXT files connected to the database were used.Results. Permanent (region of residence, age, sex, blood group, genovariants of the human leukocyte antigen HLA) and variable (indicators of cellular and humoral immunity) parameters obtained as a result of long-term immunological monitoring of persons vaccinated with the live plague vaccine according to epidemic indications have been archived. Using the information support of the Database, an assessment of the state of anti-plague immunity was carried out and screening indicators of the immune status of the contingent at risk were determined, characterizing the individual response to vaccination.Conclusions. The introduction of information technologies, which are the basis for multifactorial risk management of vaccine prevention, based on the use of modern databases for collecting, storing and analyzing data, makes it possible to make management decisions to optimize the volume and timing of measures for specific prevention of plague in the territories of natural foci of infection and in institutions that ensure the implementation of work with pathogens of especially dangerous infections.

Plague vaccines: new developments in an ongoing search.

As the reality of pandemic threats challenges humanity, exemplified during the ongoing SARS-CoV-2 infections, the development of vaccines targeting these etiological agents of disease has become increasingly critical. Of paramount concern are novel and reemerging pathogens that could trigger such events, including the plague bacterium Yersinia pestis. Y. pestis is responsible for more human deaths than any other known pathogen and exists globally in endemic regions of the world, including the four corners region and Northern California in the USA. Recent cases have been scattered throughout the world, including China and the USA, with serious outbreaks in Madagascar during 2008, 2013–2014, and, most recently, 2017–2018. This review will focus on recent advances in plague vaccine development, a seemingly necessary endeavor, as there is no Food and Drug Administration–licensed vaccine available for human distribution in western nations, and that antibiotic-resistant strains are recovered clinically or intentionally developed. Progress and recent development involving subunit, live-attenuated, and nucleic acid–based plague vaccine candidates will be discussed in this review.Key points• Plague vaccine development remains elusive yet critical.• DNA, animal, and live-attenuated vaccine candidates gain traction.

Impact of Enzootic Plague on a Population of Mexican Woodrats

Photo 1: Our controlled study of plague utilized capture–recapture to estimate survival rates of Mexican woodrats (Neotoma mexicana) in four groups comprising all combinations of vaccination, vector control, and no treatment. Photo credit: D. Biggins. Photo 2: Our study area in the Colorado foothills had many woodrat nests in shrub patches (especially three-leaf sumac, Rhus trilobata, whose leaves turned orange in fall (foreground and right side of photograph). A few nests were in cavities of cottonwoods (Populus deltoides; center). Photo credit : D. Biggins. Photo 3: Mexican woodrats are industrious nest-builders. Panel A shows a large stick nest (~ 1 m high, estimated volume 510 liters, ranked 11th largest of 139 stick nests measured) in a hawthorn (Crataegus succulenta) and sumac shrub patch. Some nests were in rock crevices (B). Photo credit : D. Biggins (A) and S. Ramakrishnan (B). Photo 4: Woodrats also constructed nests by modifying abandoned magpie (Pica hudsonia) nests (panels A and B). We infused woodrat nests on treated plots with deltamethrin dust to control vector fleas. Photo credit: D. Biggins. Photo 5: We trapped woodrats in wire mesh traps (A) and handled them under isoflurane anesthesia to collect blood samples (B), comb fleas, and take measurements, and to vaccinate a subsample of them with an experimental plague vaccine. We combed one or more fleas from 51% of the woodrats on non-dusted plots compared to a flea prevalence of 5% on dusted plots. Photo credit: S. Ramakrishnan. These photographs illustrate the article “Enzootic plague reduces survival of Mexican woodrats (Neotoma mexicana) in Colorado” by Biggins, D. E. S. Ramakrishnan, T. E. Rocke, J. L. Williamson, and J. Wimsatt published in Ecosphere. https://doi.org/10.1002/ecs2.3371.