Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response.

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization.

Two-dose "extended priming" immunization amplifies humoral immune responses by synchronizing vaccine delivery with the germinal center response.

"Extended priming" immunization regimens that prolong exposure of the immune system to vaccines during the primary immune response have shown promise in enhancing humoral immune responses to a variety of subunit vaccines in preclinical models. We previously showed that escalating-dosing immunization (EDI), where a vaccine is dosed every other day in an increasing pattern over 2 weeks dramatically amplifies humoral immune responses. But such a dosing regimen is impractical for prophylactic vaccines.