title: Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose.
abstract: In subunit vaccines, strong CD8(+) T-cell responses are desired, yet they are elusive at reasonable adjuvant doses. We show that targeting adjuvant to the lymph node (LN) via ultrasmall polymeric nanoparticles (NPs), which rapidly drain to the LN after intradermal injection, greatly enhances adjuvant efficacy at low doses. Coupling CpG-B or CpG-C oligonucleotides to NPs led to better dual-targeting of adjuvant and antigen (codelivered on separate NPs) in cross-presenting dendritic cells compared with free adjuvant. This led to enhanced dendritic cell maturation and T helper 1 (Th1)-cytokine secretion, in turn driving stronger effector CD8(+) T-cell activation with enhanced cytolytic profiles and, importantly, more powerful memory recall. With only 4 μg CpG, NP-CpG-B could substantially protect mice from syngeneic tumor challenge, even after 4 mo of vaccination, compared with free CpG-B. Together, these results show that nanocarriers can enhance vaccine efficacy at a low adjuvant dose for inducing potent and long-lived cellular immunity.
authors.affiliation: Institute of Bioengineering, School of Life Sciences and School of Engineering, Swiss Institute of Experimental Cancer Research, School of Life Sciences, and Institute of Chemical Science and Engineering, School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Titta
authors.forename: Marie
authors.initials: M
authors.lastname: Ballester
authors.forename: Ziad
authors.initials: Z
authors.lastname: Julier
authors.forename: Chiara
authors.initials: C
authors.lastname: Nembrini
authors.forename: Laura
authors.initials: L
authors.lastname: Jeanbart
authors.forename: André J
authors.initials: AJ
authors.lastname: van der Vlies
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods; D007111:Immunity, Cellular / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D009369:Neoplasms / Q000517:prevention & control*; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000378:metabolism*; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D009838:Oligodeoxyribonucleotides; D022223:Vaccines, Subunit