Deak, P. E. | Search bioRxiv

bioRxiv2025

HIV Virion Capturing Liposomes for Therapeutic Vaccination

HIV infection currently has no effective cures and requires lifelong antiretroviral treatments. Cures have failed due to HIVs immune evasion and rapid mutation rate. Here we present a first in class HIV therapeutic vaccine, termed nanotrap therapeutic vaccines (NTVs) that are designed to capture circulating HIV virions and facilitate internalization by local antigen presenting cells. NTVs are modified liposomes that display the CD4 mimetic molecule, CJF-III-288, on their surfaces and have the TLR 7/8 agonist R848 loaded into their core. We show that NTVs can 1) bind gp120 and capture pseudoviral particles, 2) facilitate uptake by antigen presenting cells and 3) generate robust anti-HIV CD8 T cell immunity in transient infection mouse models. NTVs have translational potential to generate patient-specific HIV immunity.

bioengineering↗

bioRxiv2020

Identification, Characterization, and Targeting of a Rare and Temporal Dendritic Cell State that Facilitates Adaptive Immune Responses

The heterogeneity of innate immune cells facilitates efficient antigen presentation and immune activation in the presence of pathogens via cooperativity of various cell subsets and cell states but also obscures the contribution of individual antigen presenting cells (APCs) to overall immune response.1 It has been hypothesized that a small number of APCs, which are more sensitive to the initial pathogen stimulus, are responsible for coordinating neighboring APCs in an effort to share the metabolic strain associated with heightened pathogen sensitivity.2 In this study, we have identified a temporally-controlled state of dendritic cells (DCs) that demonstrate greater sensitivity to toll-like-receptor (TLR) agonists and secrete the majority of paracrine activating cytokines (TNF, IL-6...ect). We were able to isolate this distinct population of DCs preferentially phagocytosed the majority of fluorescently labeled, TLR agonist conjugated microparticles (MPs).3 We call this population First Responder cells (FRs) due to their ability to first uptake the MPs and activate neighboring APCs via paracrine signaling. We show that FRs exist in this state for <3 hours, cycle through this state on a <24-hour timescale and show a distinct mRNA profile. Furthermore, FRs are necessary for generation of adaptive responses both in vitro and in vivo. We also show that we can improve both IgG titers and CD8 responses in vivo by targeting two highly upregulated receptors on FR cells, DAP12 and PRG2. Given the significance of FR involvement in APC activation, this study has broad immunological value because it offers a critical first evaluation of a new APC cell state but also has important translational value for improving vaccine efficacy via FR targeting.

immunology↗