Glycolipid-Containing Nanoparticle Vaccine Engages Invariant NKT Cells to Enhance Humoral Protection against Systemic Bacterial Infection but Abrogates T-Independent Vaccine Responses

佐剂 CD1D公司 肺炎链球菌 免疫系统 免疫学 糖脂 抗原 生物 表位 微生物学 T细胞 自然杀伤性T细胞 抗生素
作者
Travis Shute,Eyal Amiel,Noran Alam,Jennifer L. Yates,Katya Mohrs,Elizabeth Dudley,Briana Hauff-Salas,Chloe Mesa,Adriana Serrata,Daniel Santamaría del Ángel,Brandy A. Vincent,Amanda Weyers,Paula A. Lanthier,Emilie E. Vomhof-DeKrey,Rachel M. Fromme,Mitchell Laughlin,Olivia Z. Durham,Jianjun Miao,Devon A. Shipp,Robert J. Linhardt,Kelly Nash,Elizabeth A. Leadbetter
出处
期刊:Journal of Immunology [American Association of Immunologists]
卷期号:206 (8): 1806-1816 被引量:7
标识
DOI:10.4049/jimmunol.2001283
摘要

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.
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