ArticlePloS one2018
A panel of correlates predicts vaccine-induced protection of rats against respiratory challenge with virulent Francisella tularensis.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Transcriptional analyses of peripheral blood lymphocytes obtained shortly after primary immunization discriminate vaccines againstInfection and immunity · 2026Article
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- The immune response toFrontiers in microbiology · 2025Review
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- The rLVS ΔHuman vaccines & immunotherapeutics · 2023Article
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- IL-12p40 is essential but not sufficient for Francisella tularensis LVS clearance in chronically infected mice.PloS one · 2023Article
- Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis.NPJ vaccines · 2022Article
- Novel Transcriptional and Translational Biomarkers of Tularemia Vaccine Efficacy in a Mouse Inhalation Model: Proof of Concept.Microorganisms · 2021Article
- The O-Ag Antibody Response to Francisella Is Distinct in Rodents and Higher Animals and Can Serve as a Correlate of Protection.Pathogens (Basel, Switzerland) · 2021Article
- Modern Development and Production of a New Live Attenuated Bacterial Vaccine, SCHU S4Pathogens (Basel, Switzerland) · 2021Article
- Aim2 and Nlrp3 Are Dispensable for Vaccine-Induced Immunity against Francisella tularensis Live Vaccine Strain.Infection and immunity · 2021Article
- Characterization of Schu S4Virulence · 2020Article
- Immune lymphocytes halt replication of Francisella tularensis LVS within the cytoplasm of infected macrophages.Scientific reports · 2020Article
- Vaccine-Mediated Mechanisms ControllingPathogens (Basel, Switzerland) · 2020Article
- The Many Hosts of Mycobacteria 8 (MHM8): A conference report.Tuberculosis (Edinburgh, Scotland) · 2020Review
- Guanylate-Binding Proteins Are Critical for Effective Control ofFrontiers in cellular and infection microbiology · 2020Article
- Bacterial Vaccine Antigen Discovery in the Reverse Vaccinology 2.0 Era: Progress and Challenges.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are no defined correlates of protection for any intracellular pathogen, including the bacterium Francisella tularensis, which causes tularemia. Evaluating vaccine efficacy against sporadic diseases like tularemia using field trials is problematic, and therefore alternative strategies to test vaccine candidates like the Francisella Live Vaccine Strain (LVS), such as testing in animals and applying correlate measurements, are needed. Recently, we described a promising correlate strategy that predicted the degree of vaccine-induced protection in mice given parenteral challenges, primarily when using an attenuated Francisella strain. Here, we demonstrate that using peripheral blood lymphocytes (PBLs) in this approach predicts LVS-mediated protection against respiratory challenge of Fischer 344 rats with fully virulent F. tularensis, with exceptional sensitivity and specificity. Rats were vaccinated with a panel of LVS-derived vaccines and subsequently given lethal respiratory challenges with Type A F. tularensis. In parallel, PBLs from vaccinated rats were evaluated for their functional ability to control intramacrophage Francisella growth in in vitro co-culture assays. PBLs recovered from co-cultures were also evaluated for relative gene expression using a large panel of genes identified in murine studies. In vitro control of LVS intramacrophage replication reflected the hierarchy of protection. Further, despite variability between individuals, 22 genes were significantly more up-regulated in PBLs from rats vaccinated with LVS compared to those from rats vaccinated with the variant LVS-R or heat-killed LVS, which were poorly protective. These genes included IFN-γ, IL-21, NOS2, LTA, T-bet, IL-12rβ2, and CCL5. Most importantly, combining quantifications of intramacrophage growth control with 5-7 gene expression levels using multivariate analyses discriminated protected from non-protected individuals with greater than 95% sensitivity and specificity. The results therefore support translation of this approach to non-human primates and people to evaluate new vaccines against Francisella and other intracellular pathogens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.