1. Microbiology and Infectious Disease

A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus

  1. Elsio A Wunder  Is a corresponding author
  2. Haritha Adhikarla
  3. Camila Hamond
  4. Katharine A Owers Bonner
  5. Li Liang
  6. Camila B Rodrigues
  7. Vimla Bisht
  8. Jarlath E Nally
  9. David P Alt
  10. Mitermayer G Reis
  11. Peter J Diggle
  12. Philip L Felgner
  13. Albert Ko
  1. Department of Epidemiology of Microbial Diseases; Yale School of Public Health, United States
  2. Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Brazil
  3. Department of Medicine, Division of Infectious Disease; University of California Irvine, United States
  4. Institute of Technology in Immunobiology, Oswaldo Cruz Foundation; Brazilian Ministry of Health, Brazil
  5. Infectious Bacterial Diseases Research Unit, National Animal Disease Center, Agricultural Research Service; United States Department of Agriculture, United States
  6. CHICAS, Lancaster Medical School; Lancaster University, United Kingdom
https://doi.org/10.7554/eLife.64166
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Cite this article
  1. Elsio A Wunder
  2. Haritha Adhikarla
  3. Camila Hamond
  4. Katharine A Owers Bonner
  5. Li Liang
  6. Camila B Rodrigues
  7. Vimla Bisht
  8. Jarlath E Nally
  9. David P Alt
  10. Mitermayer G Reis
  11. Peter J Diggle
  12. Philip L Felgner
  13. Albert Ko
(2021)
A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus
eLife 10:e64166.
https://doi.org/10.7554/eLife.64166
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5 figures, 1 table and 5 additional files

Figures

Figure 1
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Dissemination of L1-130 fcpA- mutant in animal tissues.

(A) Kinetics of infection of L1-130 WT, L1-130 fcpA- vaccine, and L1-130 heat-killed vaccine in blood, kidney, liver, and brain of hamsters after inoculation with 107 bacteria. All animals infected …

Figure 1—source data 1

Raw data for dissemination experiments in hamster and mouse.

https://cdn.elifesciences.org/articles/64166/elife-64166-fig1-data1-v1.xls
Figure 2
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Efficacy of L1-130 fcpA- attenuated-vaccine model.

Animals were vaccinated with a dose of 107 leptospires (hamsters) or a range of doses from 107 to 101 leptospires (mice) by subcutaneous (SC) route. Animals were bled the day before immunization …

Figure 2—source data 1

Raw data for qPCR experiments in hamster and mouse.

https://cdn.elifesciences.org/articles/64166/elife-64166-fig2-data1-v1.xls
Figure 3
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Immunogenicity and correlates of immunity for L1-130 fcpA- attenuated-vaccine model.

Individual sera of hamsters and mice were obtained after 20 days post-vaccination by a subcutaneous (SC) dose of 107 leptospires (hamsters) or a range of doses from 107 to 101 leptospires (mice) of …

Figure 3—source data 1

Raw data for microscopic agglutination test (MAT) and passive transfer experiments in hamster and mouse, and ELISA data in mouse.

https://cdn.elifesciences.org/articles/64166/elife-64166-fig3-data1-v1.xls
Figure 4 with 2 supplements
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Proteome array analysis of immune-sera against L1-130 fcpA- attenuated-vaccine.

Using statistical modeling we calculated the t-statistics value for each individual antigen used in the proteome array (660 for hamster and 330 for mice) based on three groups: the contrast between …

Figure 4—source data 1

Raw data of proteome array experiments in hamster and mouse.

https://cdn.elifesciences.org/articles/64166/elife-64166-fig4-data1-v1.xls
Figure 4—figure supplement 1
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In-silico analysis of protein targets.

Using PSORB information and Genoscope database, we classified the 154 protein targets identified in this study by their putative localization in the cell (A) and their clusters of orthologous group (…

Figure 4—figure supplement 2
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Mouse dose–response relationship.

Analysis showing an association between the different doses of the attenuated L1-130 fcpA- attenuated-vaccine in mice and the mean signal response intensity against all different proteins.

Figure 5 with 1 supplement
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Heat-map of 41 seroreactive proteins recognized by hamsters and mice immunized with attenuated L1-130 fcpA- attenuated-vaccine.

Proteins were selected based on the groups depicted on Figure 4 and Supplementary file 4: present in all three groups of analysis (red), present in both hamster and mice immunized with 107 …

Figure 5—source data 1

Raw data of amino acid identity of 41 selected protein targets among different Leptospira species.

https://cdn.elifesciences.org/articles/64166/elife-64166-fig5-data1-v1.xls
Figure 5—figure supplement 1
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Complementary heat-map of 41 seroreactive proteins recognized by hamsters and mice immunized with attenuated L1-130 fcpA- attenuated-vaccine.

Proteins were selected based on the groups depicted on Figure 4 and Supplementary file 4: present in all three groups of analysis (red), present in both hamster and mice immunized with 107 …

Tables

Key resources table
Reagent type
(species) or resource		DesignationSource or referenceIdentifiersAdditional information
Strain, strain background (Leptospira interrogans)Fiocruz L1-130 fcpA- mutantWunder et al., 2016a doi:10.1111/mmi.13403L. interrogans serovar Copenhageni strain Fiocruz L1-130 fcpA-Fiocruz L1-130 fcpA- mutant
AntibodyPeroxidase AffiniPure Goat Anti-Mouse IgG (H+L)Jackson Immuno ResearchCat# 115-035-166 RRID:AB_2338511ELISA (1:50,000)
WB (1:100,000)
AntibodyPeroxidase AffiniPure Goat Anti-Mouse IgG (H+L)Jackson Immuno ResearchCat# 107-035-142
RRID:AB_2337454		WB (1:100,000)
AntibodyHamster α-fcpA- sera (Hamster polyclonal)This paperSee Material and methods
WB (1:100)
AntibodyHamster control sera (Hamster polyclonal)This paperSee Material and methods
WB (1:100)
Chemical compound, drugSureBlue Reserve TMB 1-Component Microwell Peroxidase SubstrateSeraCareCat. #: 5120–0081
Chemical compound, drugSulfuric Acid (H2SO4)Sigma-AldrichCat. #: 258105
Chemical compound, drugProteinase KThermo FisherCat. #: EO0491
Chemical compound, drugPlatinum Quantitative PCR Supermix-UDGThermo FisherCat. #: 11730017
Software, algorithmGraphPad Prism softwareGraphPad SoftwareRRID:SCR_015807Version 8.0.0
Software, algorithmRStudio softwareRStudioRRID:SCR_000432Version 1.0.153

Additional files

Supplementary file 1

Leptospira strains used in this study for challenge after vaccination with L1-130 fcpA- mutant.

https://cdn.elifesciences.org/articles/64166/elife-64166-supp1-v1.docx
Supplementary file 2

Efficacy of the immunization with a dose of 107 leptospires of the attenuated L1-130 fcpA- mutant in hamsters followed by challenge with 108 leptospires with homologous or heterologous strains by conjunctival route.

https://cdn.elifesciences.org/articles/64166/elife-64166-supp2-v1.docx
Supplementary file 3

Efficacy of the immunization with different doses of the attenuated L1-130 fcpA- mutant in mice followed by challenge with 108 leptospires of heterologous strain by intraperitoneal route.

https://cdn.elifesciences.org/articles/64166/elife-64166-supp3-v1.docx
Supplementary file 4

Complete list of 154 protein targets identified by the proteome array as correlates of immunity for the attenuated-vaccine model.

https://cdn.elifesciences.org/articles/64166/elife-64166-supp4-v1.xlsx
Transparent reporting form
https://cdn.elifesciences.org/articles/64166/elife-64166-transrepform-v1.docx

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