title: Sublingual injection of microparticles containing glycolipid ligands for NKT cells and subunit vaccines induces antibody responses in oral cavity.
abstract: Natural Killer T (NKT) cells are a unique type of innate immune cells which exert paradoxical roles in animal models through producing either Th1 or Th2 cytokines and activating dendritic cells. Alpha-galactosylceramide (αGalCer), a synthetic antigen for NKT cells, was found to be safe and immune stimulatory in cancer and hepatitis patients. We recently developed microparticle-formulated αGalCer, which is selectively presented by dendritic cells and macrophages, but not B cells, and thus can avoid the anergy of NKT cells. In this study, we have examined the immunogenicity of microparticles containing αGalCer and protein vaccine components through sublingual injection in mice. The results showed that sublingual injection of microparticles containing αGalCer and ovalbumin triggered IgG responses in serum (titer >1:100,000), which persisted for more than 3months. Microparticles containing ovalbumin alone also induced comparable level of IgG responses. However, immunoglobulin subclass analysis showed that sublingually injected microparticles containing αGalCer and ovalbumin induced 20 fold higher Th1 biased antibody (IgG2c) than microparticles containing OVA alone (1:20,000 as compared to 1:1000 titer). Sublingual injection of microparticles containing αGalCer and ovalbumin induced secretion of both IgG (titer >1:1000) and IgA (titer=1:80) in saliva secretion, while microparticles containing ovalbumin alone only induced secretion of IgG in saliva. Our results suggest that sublingual injection of microparticles and their subsequent trafficking to draining lymph nodes may induce adaptive immune responses in mucosal compartments. Ongoing studies are focused on the mechanism of antigen presentation and lymphocyte biology in the oral cavity, as well as the toxicity and efficacy of these candidate microparticles for future applications.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: DeLyria
authors.affiliation: Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. Electronic address: dapengzhoulab@tongji.edu.cn.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Shailbala
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States; Shanghai Public Health Clinical Center, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Fenge
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai, China.
authors.forename: Hongzhou
authors.initials: H
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, United States.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, United States.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D005699:Galactosylceramides / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood* / Q000276:immunology; D007267:Injections; D008024:Ligands; D051379:Mice; D008863:Microspheres; D009055:Mouth / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D010316:Particle Size; D019809:Streptavidin / Q000737:chemistry; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D005699:Galactosylceramides; D007136:Immunoglobulins; D008024:Ligands; D022223:Vaccines, Subunit; C493154:alpha-galactosylceramide; D019809:Streptavidin
keywords: Alpha-galactosylceramide; Antibody class switch; Microparticles; Mucosal immunity; Natural Killer T cells; Vaccines