Although replication-competent adenovirus (Ad) vectors are promising in AIDS vaccine design, their safety in immune compromised hosts is unknown. To initially address this question, enteric-coated tablets containing a replicating Ad vector were orally administered to SHIV- and SIV-infected rhesus macaques with normal, intermediate or low CD4 T cell counts and stable disease. The vector was detected within a week after tablet administration in stools of all animals but not in nasal secretions, indicating no spread of virus to the upper respiratory tract. CD4 T cell counts and viral loads remained stable in all animals and no signs of fever, weight loss, or other clinical symptoms of Ad-induced disease were observed during 10 weeks of follow-up. Oral delivery of the replicating Ad vector was safe and well tolerated by SHIV- and SIV-infected hosts. Oral enteric-coated tablets may prove safe for administering replicating Ad-vectored vaccines in areas with high HIV prevalence.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.vaccine.2006.03.048 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lipid-encapsulated gold nanoparticles: an advanced strategy for attenuating the inflammatory response in SARS-CoV-2 infection.
J Nanobiotechnology
January 2025
Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-Si, 17104, Gyeonggi-Do, Republic of Korea.
Background: Nanodrugs play a crucial role in biomedical applications by enhancing drug delivery. To address safety and toxicity concerns associated with nanoparticles, lipid-nanocarrier-based drug delivery systems have emerged as a promising approach for developing next-generation smart nanomedicines. Ginseng has traditionally been used for various therapeutic purposes, including antiviral activity.
View Article and Find Full Text PDFSuccessful oral RNA interference efficiency in the silkworm Bombyx mori through nanoparticle-shielded dsRNA delivery.
J Insect Physiol
January 2025
Institute of Biosciences and Applications, National Centre for Scientific Research Demokritos, Athens, Greece.
Double-stranded RNA (dsRNA) mediated RNA interference (RNAi) is a tool in functional gene study and pest control. However, RNAi efficiency in Lepidoptera is low compared to the RNAi sensitive Coleoptera. Previous studies on RNAi in the silkworm Bombyx mori, the lepidopteran model insect, were performed by injection only.
View Article and Find Full Text PDFCritical updates on oral insulin drug delivery systems for type 2 diabetes mellitus.
J Nanobiotechnology
January 2025
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, leading to elevated blood sugar levels. Exogenous insulin can counteract the diminished response to insulin and effectively controlling blood glucose levels, thereby minimizing diabetes-related complications. However, given the injectable nature of exogenous insulin, apprehensions regarding its safety and the difficulties associated with its administration have hindered its widespread and prompt utilization.
View Article and Find Full Text PDFZinc nanoparticles from oral supplements accumulate in renal tumours and stimulate antitumour immune responses.
Nat Mater
January 2025
Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
A successful therapeutic outcome in the treatment of solid tumours requires efficient intratumoural drug accumulation and retention. Here we demonstrate that zinc gluconate in oral supplements assembles with plasma proteins to form ZnO nanoparticles that selectively accumulate into papillary Caki-2 renal tumours and promote the recruitment of dendritic cells and cytotoxic CD8 T cells to tumour tissues. Renal tumour targeting is mediated by the preferential binding of zinc ions to metallothionein-1X proteins, which are constitutively overexpressed in Caki-2 renal tumour cells.
View Article and Find Full Text PDFEvaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.
J Med Chem
January 2025
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!