Nanoparticle immunoadjuvant complexes augment antigen-specific germinal center responses

ABSTRACT: A strategy for improving protective humoral immunity against infectious diseases is to directly modulate the germinal center (GC) through immunogen design, such as germline targeting. However, there remains a critical need for next generation vaccine approaches to elicit improved GC responses resulting in increased antibody specificity, diversity, and durability. Here, we investigated whether a cytokine could be scaffolded on nanoparticles to enhance antigen-specific GC responses and drive maturation of B cell lineages. We designed a chimeric nanoparticle using the GT8-60mer, a germline-targeting HIV immunogen, as a model to scaffold IL-21, a canonical GC cytokine. Delivered using plasmid DNA, nanoparticle immunoadjuvant complexes (NICs) scaffolding GT8 and IL-21 (GT8-IL-21-NIC) drove improved serum antibody titers, antigen-specific GC B cells, and functional Tfh cell responses relative to antigen-only nanoparticles and to co-delivery of IL-21 monomer. Immunization with the GT8-IL-21-NIC also improve humoral immune response durability, with improved bone marrow plasma cell responses. Transcriptomic analysis of GT8-specific GC B cells from GT8-IL-21-NIC immunized mice demonstrated upregulation of selection-associated gene signatures. Utilizing mice harboring human VRC01-class bnAb precursor heavy and light chain genes, immunization with the GT8-IL-21-NIC led to enhanced GC responses with increased antibody diversity, clonal expansion, and somatic hypermutation, with B cells acquiring an increased number of key VRC01-class broadly neutralizing antibody mutations. Thus, generating NICs using IL-21 may provide value as a tool to improve antigen-specific GC responses and vaccine-induced immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE311626 | GEO | 2026/03/18

REPOSITORIES: GEO