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Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.

Publication ,  Journal Article
Lin, Y-Y; Belle, I; Blasi, M; Huang, M-N; Buckley, AF; Rountree, W; Klotman, ME; Cara, A; Negri, D
Published in: Mol Ther Methods Clin Dev
June 12, 2020

We previously developed integrase-defective lentiviral vectors (IDLVs) as an antigen delivery system for inducing strong and prolonged immunity in animal models. Here, we examined the association between persistence of antigen expression and durability of immune response. Following a single intramuscular (i.m.) or subcutaneous (s.c.) injection of IDLV delivering GFP in mice, we evaluated antigen expression and inflammation at the site of injection and persistence of antigen-specific T cells at early and late time points. Durable antigen expression was detected up to 90 days only after i.m. immunization. Mononuclear inflammation was evident soon after IDLV injection in both i.m. and s.c. immunized mice, but remained detectable up to 30 days postinjection only in i.m. immunized mice. Similarly, GFP-specific T cells were more persistent in the i.m. immunized mice. Interestingly, GFP+ muscle fibers were co-expressing major histocompatibility complex (MHC) class I, suggesting that muscle cells are competent for presenting antigens to T cells in vivo. In in vitro experiments, we demonstrated that although both primary myoblasts and myocytes present the antigen to GFP-specific T cells through MHC class I, myoblasts are more resistant to Fas-dependent cytotoxic T lymphocyte (CTL) killing activity. Overall, these data indicate that muscle cells may serve as an antigen reservoir that contributes to the long-term immunity induced by IDLV vaccination.

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Published In

Mol Ther Methods Clin Dev

DOI

ISSN

2329-0501

Publication Date

June 12, 2020

Volume

17

Start / End Page

532 / 544

Location

United States

Related Subject Headings

  • 3206 Medical biotechnology
 

Citation

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Lin, Y.-Y., Belle, I., Blasi, M., Huang, M.-N., Buckley, A. F., Rountree, W., … Negri, D. (2020). Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity. Mol Ther Methods Clin Dev, 17, 532–544. https://doi.org/10.1016/j.omtm.2020.03.008
Lin, Yi-Yu, Ian Belle, Maria Blasi, Min-Nung Huang, Anne F. Buckley, Wes Rountree, Mary E. Klotman, Andrea Cara, and Donatella Negri. “Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.Mol Ther Methods Clin Dev 17 (June 12, 2020): 532–44. https://doi.org/10.1016/j.omtm.2020.03.008.
Lin Y-Y, Belle I, Blasi M, Huang M-N, Buckley AF, Rountree W, et al. Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity. Mol Ther Methods Clin Dev. 2020 Jun 12;17:532–44.
Lin, Yi-Yu, et al. “Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.Mol Ther Methods Clin Dev, vol. 17, June 2020, pp. 532–44. Pubmed, doi:10.1016/j.omtm.2020.03.008.
Lin Y-Y, Belle I, Blasi M, Huang M-N, Buckley AF, Rountree W, Klotman ME, Cara A, Negri D. Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity. Mol Ther Methods Clin Dev. 2020 Jun 12;17:532–544.
Journal cover image

Published In

Mol Ther Methods Clin Dev

DOI

ISSN

2329-0501

Publication Date

June 12, 2020

Volume

17

Start / End Page

532 / 544

Location

United States

Related Subject Headings

  • 3206 Medical biotechnology