Vaccine approaches capable of eliciting enhanced germinal center (GC) responses would result in improved protective humoral immunity against infectious diseases. Here, we investigate whether a cytokine can be scaffolded onto a self-assembling nanoparticle immunogen to enhance antigen-specific GC responses and B cell maturation. To test this approach, we design chimeric nanoparticles bearing eOD-GT8, a germline-targeting HIV immunogen, and IL-21, a canonical GC cytokine. DNA delivery of these nanoparticle immunoadjuvant complexes (GT8-IL-21-NICs) drives improved serum antibody titers and antigen-specific GC B cell responses in mice. Transcriptomic analysis of eOD-GT8-specific GC B cells demonstrates upregulation of selection-associated gene signatures with GT8-IL-21-NIC immunization. In mice harboring human bnAb precursor heavy and light chain genes, immunization with the GT8-IL-21-NIC leads to increased antibody diversity, clonal expansion, somatic hypermutation, and the acquisition of key antibody mutations. These results highlight IL-21 as a promising genetic adjuvant and demonstrate that NICs may be a valuable tool to improve antigen-specific GC responses and vaccine-induced immunity.
Tursi et al. (Wed,) studied this question.