Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses

Biomaterials. 2019 Sep:216:119268. doi: 10.1016/j.biomaterials.2019.119268. Epub 2019 Jun 12.


Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.

Keywords: Adjuvant; Catechol; Nanocomposite hydrogel; Single-injection vaccine; Vaccine delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Chitosan / administration & dosage*
  • Chitosan / pharmacology
  • Drug Delivery Systems
  • Immunity, Humoral / drug effects*
  • Injections
  • Mice
  • Mice, Inbred C57BL
  • Nanogels / administration & dosage*
  • Ovalbumin / administration & dosage*
  • Ovalbumin / pharmacology
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / pharmacology


  • Adjuvants, Immunologic
  • N-trimethyl chitosan chloride
  • Nanogels
  • Vaccines, Subunit
  • Ovalbumin
  • Chitosan