eCD4-Ig / Emmune - LARVOL DELTA

T-cell responses shape infant SIV reservoirs and post-intervention control following AAV9-eCD4-Ig and latency reversal. (PubMed, JCI Insight) - "Controllers also exhibited higher frequencies and greater polyfunctionality of virus-specific CD8+ T-cells prior to ATI. These findings implicate immune control of reservoir size and post-ART viral dynamics in early-treated infants and suggest that AAV9-eCD4-IgG1 + AZD5582 increases the likelihood of post-ART viral control."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

In vivo HSC gene therapy enables sustained eCD4-Ig expression for SIV prevention. (PubMed, Mol Ther Adv) - "Further improvements in protective efficacy may be achieved through approaches identified in this study, including lineage-specific expression, reduced immunogenicity, and efficient selection. These findings validate HDAd 6/3+ as a promising platform for durable gene-based delivery of biologic therapeutics and guide advancement of HSC gene therapy for HIV and other chronic infections."

Journal • Preclinical • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • CD4

In vivo evolution of env in SHIV-AD8EO-infected rhesus macaques after AAV-vectored delivery of eCD4-Ig. (PubMed, Mol Ther) - "This resistance was not driven by decreased CD4 affinity, subverted sulfopeptide mimicry, changes to coreceptor tropism, or by a gain of CD4 independence. Rather, our data argue that the Env evolving in this animal attained eCD4-Ig resistance by decreasing triggerability, stabilizing state-2, and changing the nature of its relationship to the host CD4."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Generation of Highly Potent HIV/SIV Neutralizing Molecules after In Vivo HSC Transduction of Rhesus Macaques with a Novel HDAd Strategy (ASGCT 2024) - "HSCs were mobilized using AMD3100 and G-CSF followed by intravenous infusion of integrating HDAd vectors. Here, we use an improved HDAd platform (HDAd6/3+-cxcr4), which is 10x more efficient than prior HDAds, to deliver an enhanced eCD4-Ig variant ("eCD4-Ig-Emm006") that maintains high potency in vivo. These data highlight the HDAd platform's capabilities as a promising drug-delivery approach for infectious disease prevention and management."

Preclinical • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • CD4 • CXCR4