Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
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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.
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.;
Journal of Immunology, 206, 1806–1816; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Journal of Immunology; https://harc.rpi.edu/;