Global Phase IIb/III Microbicide Clinical Trials

<div><p><b>Red circle:</b> Carraguard. Sponsored by Population Council. Phase III study of the efficacy and safety of the microbicide Carraguard in preventing HIV seroconversion in women.</p> <p><b>Blue cross: 2% and 0.5% PRO2000.</b> Sponsored by Microbicide Development Programme. A phase III, multi-centre, randomised, double-blind, placebo-controlled trial to evaluate the effectiveness and safety of 0.5% PRO2000 and 2% PRO2000 gels for the prevention of vaginally acquired HIV infection.</p> <p><b>Yellow cross: BufferGel and 0.5% PRO2000.</b> Sponsored by US National Institutes of Health. HPTN 035: Phase II/IIb safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 gel (P) for the prevention of HIV infection in women.</p> <p><b>Green star: Cellulose sulphate—East and Southern Africa.</b> Sponsored by CONRAD. Randomised controlled trial of 6% cellulose sulphate gel and the effect on vaginal HIV transmission.</p> <p><b>Green star: Cellulose sulphate—Nigeria.</b> Sponsored by Family Health International. Phase III trial of cellulose sulphate for HIV prevention. <b>Pink box: C31G (SAVVY).</b> Sponsored by Family Health International. Phase III trial of SAVVY in Ghana and Nigeria.</p></div

DataSheet_1_Evaluation of dendritic cell-targeting T7 phages as a vehicle to deliver avian influenza virus H5 DNA vaccine in SPF chickens.docx

IntroductionThere is a growing demand for effective technologies for the delivery of antigen to antigen-presenting cells (APCs) and their immune-activation for the success of DNA vaccines. Therefore, dendritic cell (DC)-targeting T7 phages were used as a vehicle to deliver DNA vaccine.MethodsIn this study, a eukaryotic expression plasmid pEGFP-C1-HA2-AS containing the HA2 gene derived from the avian H5N1 virus and an anchor sequence (AS) gene required for the T7 phage packaging process was developed. To verify the feasibility of phage delivery, the plasmid encapsulated in DC-targeting phage capsid through the recognition of AS was evaluated both in vitro and in vivo. The pEGFP-C1-HA2-AS plasmid could evade digestion by DNase I by becoming encapsulated into the phage particles and efficiently expressed the HA2 antigen in DCs with the benefit of DC-targeting phages.ResultsFor chickens immunized with the DC-targeting phage 74 delivered DNA vaccine, the levels of IgY and IgA antibodies, the concentration of IFN-γ and IL-12 cytokines in serum, the proliferation of lymphocytes, and the percentage of CD4+/CD8+ T lymphocytes isolated from peripheral blood were significantly higher than chickens which were immunized with DNA vaccine that was delivered by non-DC-targeting phage or placebo (pConclusionThis study provides a strategy for development of a novel avian influenza DNA vaccine and demonstrates the potential of DC-targeting phage as a DNA vaccine delivery vehicle.</p