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

Charles B. Chesson, Matthew Huante, Rebecca J. Nusbaum, Aida G. Walker, Tara M. Clover, Jagannath Chinnaswamy, Janice Endsley, Jai S. Rudra

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number12519
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Mycobacterium bovis
Mycobacterium tuberculosis
Cellular Immunity
Nanofibers
Peptides
T-Lymphocytes
Lung
T-Lymphocyte Epitopes
Interleukin-2
Immunity
Vaccines
CD8 Antigens
Toll-Like Receptor 2
Subunit Vaccines
Bacterial Load
Aerosols
Population
Immunization
Vaccination
Antigens

ASJC Scopus subject areas

  • General

Cite this

Chesson, C. B., Huante, M., Nusbaum, R. J., Walker, A. G., Clover, T. M., Chinnaswamy, J., ... Rudra, J. S. (2018). Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis. Scientific Reports, 8(1), [12519]. https://doi.org/10.1038/s41598-018-31089-y

Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis. / Chesson, Charles B.; Huante, Matthew; Nusbaum, Rebecca J.; Walker, Aida G.; Clover, Tara M.; Chinnaswamy, Jagannath; Endsley, Janice; Rudra, Jai S.

In: Scientific Reports, Vol. 8, No. 1, 12519, 01.12.2018.

Research output: Contribution to journalArticle

Chesson, Charles B. ; Huante, Matthew ; Nusbaum, Rebecca J. ; Walker, Aida G. ; Clover, Tara M. ; Chinnaswamy, Jagannath ; Endsley, Janice ; Rudra, Jai S. / Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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