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

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2022 Aug 26

PMID 36028220

Authors

Soumik Barman

Francesco Borriello

Byron Brook

Carlo Pietrasanta

Maria De Leon

Cali Sweitzer

Manisha Menon

Simon D van Haren

Dheeraj Soni

Yoshine Saito

Etsuro Nanishi

Sijia Yi

Sharan Bobbala

Ofer Levy

Evan A Scott

David J Dowling

Affiliations

Soon will be listed here.

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 (T) 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.

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