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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-12, Vol.110 (49), p.19902-19907
Main Authors: de Titta, Alexandre, Ballester, Marie, Julier, Ziad, Nembrini, Chiara, Jeanbart, Laura, van der Vlies, André J., Swartz, Melody A., Hubbell, Jeffrey A.
Format: Article
Language:English
Subjects:
adjuvants
Adjuvants, Immunologic - metabolism
Animals
Antigens
Biological Sciences
CD4-positive T-lymphocytes
CD8-Positive T-Lymphocytes - immunology
cell-mediated immunity
Cells
Dendritic cells
Drug Delivery Systems - methods
Immunity, Cellular - immunology
Immunologic Memory - immunology
Injections, Intradermal
lymph nodes
Lymph Nodes - cytology
Memory
Memory recall
Mice
nanocarriers
Nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - metabolism
Natural killer T cells
Neoplasms - prevention & control
Oligodeoxyribonucleotides - immunology
Oligodeoxyribonucleotides - metabolism
oligonucleotides
Ova
Recall
Secretion
subunit vaccines
T lymphocytes
Tumors
Vaccination
Vaccines
Vaccines, Subunit - immunology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1313152110