Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Alexandre De Titta, Marie Ballester, Ziad Julier, Chiara Nembrini, Laura Jeanbart, André J. Van Der Vlies, Melody A. Swartz, Jeffrey A. Hubbell

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148 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19902-19907
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number49
DOIs
StatePublished - Dec 3 2013

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De Titta, A., Ballester, M., Julier, Z., Nembrini, C., Jeanbart, L., Van Der Vlies, A. J., Swartz, M. A., & Hubbell, J. A. (2013). Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose. Proceedings of the National Academy of Sciences of the United States of America, 110(49), 19902-19907. https://doi.org/10.1073/pnas.1313152110