Data from: Genome-wide epitope mapping reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection
Creators
- 1. University of Copenhagen
- 2. Moredun Research Institute
- 3. Wageningen University & Research
- 4. Nimble Therapeutics, Inc.*
- 5. Ministry of Agriculture, Nature and Food Quality
Description
Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of infection. Vaccination is a key control measure and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin preparations. Subunit vaccines based on recombinant proteins offer significant advantages, as they can be designed to reduce reactogenicity and can be co-designed with defined antigen serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 ORFs in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different C. burnetii exposure statuses. However, C. burnetii exposure did result in more uniform seroreactivity across species. Through the implementation of three different vaccine candidate methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic, out of which 65 have been previously described. This is the first study to investigate seroreactivity against the entire C. burnetii genome presented as overlapping linear peptides and provides the basis for selection of antigen targets for next generation Q fever vaccines and diagnostic tests.
Notes
Aggregated microarray data for all samples:
microarray_data_aggregated.txt
Fluorescence intensity values for each peptide on the microarray microarray are found in an aggregated tab-seperated file format. First column contains the synthesized peptide sequences, second column contains the peptide group:
- EXPR_HHV5: HHV5-derived peptides
- EXPR_MAIN_REP1/2: C. burnetii and tetanus toxin protein derived peptides
- EXPR_NEG_CTRL_REP1/2: The random peptides
The remaining columns contain the fluorescence intensity values extracted for each of the 156 serum samples. The column names correspond to the microarray identifier (ID).
Peptide to protein mapper file:
peptide_map.txt
The peptide parent protein names and their locations are found in a tab-seperated file format. First column contains the synthesized peptide sequences, second column the name of their parent proteins, third column the length of the parent proteins, and fourth and fifth columns the start and coordinates of the peptides in their parent protein.
Serum sample metadata:
sample_metadata.txt
Information regarding the species and treatment/status of the individuals when sera were sampled are found in a tab-seperated file format. The first column contains the treatment/status of the individuals:
- NEG: C. burnetii negative
- POS: C. burnetii positive
- PC: post C. burnetii challenge
- PV1: post C. burnetii phase I vaccination
- PV2: post C. burnetii phase II vaccination
- UV + C: unvaccinated C. burnetii challenged
- PV1/2 + C: C. burnetii phase I/II vaccinee challenged
Second column are numeric identifiers for the individuals, third column the dates sera were sampled if recorded (missing dates are denoted by "n/a"), fourth column the species of the individuals, and fifth column the ID of the microarray the individual sera were incubated with (corresponds to the column names in microarray_data_aggregated.txt).
Funding provided by: Department of Health and Social Care
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100000276
Award Number: BB/R019975/1