Glycolipid-containing nanoparticle vaccine engages invariant NKT cells to enhance humoral protection against systemic bacterial infection but abrogates T-independent vaccine responses

Authors
Shute, Travis
Amiel, Eyal
Alam, Noran
Yates, Jennifer L.
Mohrs, Katya
Dudley, Elizabeth
Salas, Briana
Mesa, Chloe
Serrata, Adriana
Angel, Daniel
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2021-04-15
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
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Full Citation
Glycolipid-containing nanoparticle vaccine engages invariant NKT cells to enhance humoral protection against systemic bacterial infection but abrogates T-independent vaccine responses, T. Shute, E. Amiel, N. Alam, J. L. Yates, K. Mohrs, E. Dudley, B. Salas, C. Mesa, A. Serrata, D. Angel, B. K. Vincent, A. Weyers, P. A. Lanthier, E. Vomhof-Dekrey, R. Fromme, M. Laughlin, O. Durham, J. Miao, D. Shipp, R. J. Linhardt, K. Nash, E. A. Leadbetter, Journal of Immunology, 206, 1806–1816, 2021.
Abstract
CD4+ T cells enable the critical B cell humoral immune protection afforded by most effective vaccines. We and others have recently identified an alternative source of help for B cells in mice, invariant NK T (iNKT) cells. iNKT cells are innate glycolipid-specific T cells restricted to the nonpolymorphic Ag-presenting molecule CD1d. As such, iNKT cells respond to glycolipids equally well in all people, making them an appealing adjuvant for universal vaccines. We tested the potential for the iNKT glycolipid agonist, α-galactosylceramide (αGC), to serve as an adjuvant for a known human protective epitope by creating a nanoparticle that delivers αGC plus antigenic polysaccharides from Streptococcus pneumoniae αGC-embedded nanoparticles activate murine iNKT cells and B cells in vitro and in vivo, facilitate significant dose sparing, and avoid iNKT anergy. Nanoparticles containing αGC plus S. pneumoniae polysaccharides elicits robust IgM and IgG in vivo and protect mice against lethal systemic S. pneumoniae However, codelivery of αGC via nanoparticles actually eliminated Ab protection elicited by a T-independent S. pneumoniae vaccine. This is consistent with previous studies demonstrating iNKT cell help for B cells following acute activation, but negative regulation of B cells during chronic inflammation. αGC-containing nanoparticles represent a viable platform for broadly efficacious vaccines against deadly human pathogens, but their potential for eliminating B cells under certain conditions suggests further clarity on iNKT cell interactions with B cells is warranted.
Description
Journal of Immunology, 206, 1806–1816
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Journal of Immunology
https://harc.rpi.edu/
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