An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosis Article Swipe
Sasha E. Larsen
,
Jesse H. Erasmus
,
Valerie A. Reese
,
Tiffany Pecor
,
Jacob Archer
,
Amit Kandahar
,
Fan‐Chi Hsu
,
Katrina Nicholes
,
Steven G. Reed
,
Susan L. Baldwin
,
Rhea N. Coler
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/vaccines11010130
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/vaccines11010130
Mycobacterium tuberculosis (M.tb), a bacterial pathogen that causes tuberculosis disease (TB), exerts an extensive burden on global health. The complex nature of M.tb, coupled with different TB disease stages, has made identifying immune correlates of protection challenging and subsequently slowing vaccine candidate progress. In this work, we leveraged two delivery platforms as prophylactic vaccines to assess immunity and subsequent efficacy against low-dose and ultra-low-dose aerosol challenges with M.tb H37Rv in C57BL/6 mice. Our second-generation TB vaccine candidate ID91 was produced as a fusion protein formulated with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion) or as a novel replicating-RNA (repRNA) formulated in a nanostructured lipid carrier. Protein subunit- and RNA-based vaccines preferentially elicit cellular immune responses to different ID91 epitopes. In a single prophylactic immunization screen, both platforms reduced pulmonary bacterial burden compared to the controls. Excitingly, in prime-boost strategies, the groups that received heterologous RNA-prime, protein-boost or combination immunizations demonstrated the greatest reduction in bacterial burden and a unique humoral and cellular immune response profile. These data are the first to report that repRNA platforms are a viable system for TB vaccines and should be pursued with high-priority M.tb antigens containing CD4+ and CD8+ T-cell epitopes.
Related Topics
Concepts
Mycobacterium tuberculosis
Adjuvant
Immune system
Tuberculosis
Antigen
Virology
Epitope
Immunology
Tuberculosis vaccines
Immunity
Immunization
Biology
Medicine
Pathology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/vaccines11010130
- https://www.mdpi.com/2076-393X/11/1/130/pdf?version=1673927523
- OA Status
- gold
- Cited By
- 61
- References
- 70
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4313559172
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4313559172Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/vaccines11010130Digital Object Identifier
- Title
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An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-01-05Full publication date if available
- Authors
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Sasha E. Larsen, Jesse H. Erasmus, Valerie A. Reese, Tiffany Pecor, Jacob Archer, Amit Kandahar, Fan‐Chi Hsu, Katrina Nicholes, Steven G. Reed, Susan L. Baldwin, Rhea N. ColerList of authors in order
- Landing page
-
https://doi.org/10.3390/vaccines11010130Publisher landing page
- PDF URL
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https://www.mdpi.com/2076-393X/11/1/130/pdf?version=1673927523Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/2076-393X/11/1/130/pdf?version=1673927523Direct OA link when available
- Concepts
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Mycobacterium tuberculosis, Adjuvant, Immune system, Tuberculosis, Antigen, Virology, Epitope, Immunology, Tuberculosis vaccines, Immunity, Immunization, Biology, Medicine, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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61Total citation count in OpenAlex
- Citations by year (recent)
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2025: 24, 2024: 27, 2023: 10Per-year citation counts (last 5 years)
- References (count)
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70Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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