Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis

  • Sci Rep. 2018 Aug 21;8(1):12519. doi: 10.1038/s41598-018-31089-y.
Charles B Chesson  1 ,  Matthew Huante  2 ,  Rebecca J Nusbaum  3 ,  Aida G Walker  2  4 ,  Tara M Clover  4 ,  Jagannath Chinnaswamy  5 ,  Janice J Endsley  6  7 ,  Jai S Rudra  8  9
Affiliations
  • 1. Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08823, USA.
  • 2. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  • 3. Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 4. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, 77555, Texas, USA.
  • 5. Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • 6. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. [email protected].
  • 7. Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, 77555, USA. [email protected].
  • 8. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, 77555, Texas, USA. [email protected].
  • 9. Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, 77555, USA. [email protected].
PMID: 30131591 DOI: 10.1038/s41598-018-31089-y
Abstract

Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk and enhanced control of active Mtb Infection. Since boosting with BCG is contraindicated, booster vaccines that augment T cell immunity in the lungs of BCG-vaccinated individuals are urgently needed. We developed a vaccination strategy based on self-assembling peptide nanofibers presenting Mtb-specific CD8+ or CD4+ T cell epitopes that induce high frequency and antigen-specific effector memory T cells producing IFN-γ and IL-2. Intranasal immunization with peptide nanofibers was well tolerated in mice leading to increased antigen-specific CD8+ T cell population in the lungs. Co-assembled nanofibers of CD8+ T cell epitopes and Toll-like Receptor 2 (TLR2) agonists induced a 8-fold expansion in multifunctional CD8+ T cell populations in the lungs of vaccinated mice. Aerosol challenge with Mtb in BCG-primed and nanofiber-boosted mice provided an additional 0.5-log CFU reduction in lung Bacterial load and indicating enhanced protection compared to BCG alone. Together, these data suggest that heterologous prime-boost with BCG and peptide nanofiber vaccines induces cell mediated immunity in the lung, reduces Bacterial burden, and is a potentially safer alternative for boosting BCG-primed immunity.

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