Parallel conduction of the phase I preventive and therapeutic trials based on the Tat vaccine candidate.

The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).

A new dynamic endonasal stent for bilateral congenital choanal atresia.

The Authors describe a new dynamic endonasal Teflon stent, nick-named "little gun", used after the surgical transnasal endoscopic treatment of bilateral choanal atresia in a 4-day-old male. This Teflon stent, conceived to perfectly fit the new naso-choanal openings and to achieve an "orthopaedic" tutorial function, is made of three portions: "A", the barrel, "B", the breech, "C" the butt. The butt is the active part of the splint and must be rolled up around itself, in order to create a spiral tube, fitting to the new choanal openings, able to expand laterally on account of its intrinsic elastic resilience.

Papillomatosis of the larynx: treatment with CO2 laser.

OBJECTIVES: We report our experience treating papillomatosis of the larynx using CO2 laser which has a lower risk of post surgical complications. Papillomatosis has a high incidence of recurrence after surgical treatment. METHODS: We treated 42 patients (10 adults and 32 children) affected by multiple papillomatosis of the larynx. Smaller papillomas were vaporized with a 7-8 Watt CO2 laser and larger papillomas were resected at the base of their implantation. A strict follow-up during the first 3 years after surgical treatment was necessary to manage recurrences with CO2 laser endoscopy. RESULTS: All patients presented with recurrences after the first surgical treatment, but within 18-60 months all patients presented a solution of their pathology. Post-operative complications were observed in patients who did not comply with the strict follow-up protocol and presented with large lesions requiring more invasive surgery. CONCLUSIONS: CO2 laser endoscopy, although it did not prevent recurrences of papillomatosis in the larynx, is a valid surgical approach in the management of this pathology.

Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL.

The immunotherapeutic potential of biologically active HIV-1 Tat protein coupled to autologous red blood cells (RBCs) was evaluated in a mouse model. HIV-1 Tat expressed in Escherichia coli and purified to homogeneity was found to be active in viral trans activation and efficiently internalised by monocyte-derived dendritic cells (MDDCs). The product of HIV-Tat biotinylation and coupling to RBCs by means of a biotin-avidin-biotin bridge, (RBC-Tat), showed no trans activation activity and was still efficiently internalized by MDDCs as compared to uncoupled Tat.Balb/c mice were then immunized with 10 microg of soluble Tat in complete Freund's adjuvant or with 40 ng of Tat coupled on RBCs surface and boosted at week 3, 6 and 25 with 5 microg soluble Tat in incomplete Freund's adjuvant or with 20 ng of RBC-coupled Tat, respectively. Anti-Tat antibody response was similar in both groups; however, 2/6 animals immunized with soluble Tat and 6/6 animals immunized with RBC-Tat developed anti-Tat neutralizing antibodies. In addition, at week 28 cytolytic anti-Tat CTLs were detected in all animals although they were slightly higher in mice immunized with RBC-Tat. These results indicate that RBC-mediated delivery of HIV-1 Tat, in amounts 250 times lower than soluble Tat, is safe and induces specific CTL responses and neutralizing antibodies.