Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers

ACS Chem Biol. 2022 Sep 16;17(9):2559-2571. doi: 10.1021/acschembio.2c00497. Epub 2022 Aug 26.

Abstract

Adjuvanted nanocarrier-based vaccines hold substantial potential for applications in novel early-life immunization strategies. Here, via mouse and human age-specific in vitro modeling, we identified the combination of a small-molecule STING agonist (2'3'-cyclic GMP-AMP, cGAMP) and a TLR7/8 agonist (CL075) to drive the synergistic activation of neonatal dendritic cells and precision CD4 T-helper (Th) cell expansion via the IL-12/IFNγ axis. We further demonstrate that the vaccination of neonatal mice with quadrivalent influenza recombinant hemagglutinin (rHA) and an admixture of two polymersome (PS) nanocarriers separately encapsulating cGAMP (cGAMP-PS) and CL075 (CL075-PS) drove robust Th1 bias, high frequency of T follicular helper (TFH) cells, and germinal center (GC) B cells along with the IgG2c-skewed humoral response in vivo. Dual-loaded cGAMP/CL075-PSs did not outperform admixed cGAMP-PS and CL075-PS in vivo. These data validate an optimally designed adjuvantation system via age-selected small-molecule synergy and a multicomponent nanocarrier formulation as an effective approach to induce type 1 immune responses in early life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Hemagglutinins*
  • Humans
  • Immunization
  • Interleukin-12
  • Mice
  • Toll-Like Receptor 7*
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Hemagglutinins
  • Toll-Like Receptor 7
  • Interleukin-12