European Union and EDCTP strategy in the global context: recommendations for preventive HIV/AIDS vaccines research.

The European Commission (EC) has strong commitments and recognises the need to continue to ensure that HIV/AIDS research efforts receive global attention. The EC is facing this challenge in a global context and has made substantial investments together with European Developing Countries Clinical Trial Partnership (EDCTP) to formulate a program for the accomplishment of a scientific strategic plan promoting the European/African HIV vaccine development approach. The EC and EDCTP has convened a number of meetings by experts in basic and clinical virology, immunology, epidemiology, as well as industrial and regulatory representatives. The remit of the committee of experts was to define (1) objective criteria for selection of HIV candidates; (2) to determine criteria for selection of sites for clinical trials in Europe and Africa. The resulting consensus paper will guide the EC and EDCTP in developing HIV vaccine strategy and recommendations.

Flow cytometry analysis of immune cell populations isolated from cervicovaginal secretions of cynomolgus monkeys.

Flow cytometric analysis was used in this study to characterize the lymphocyte population present in the vaginal mucosa of the cynomolgus monkey. Vaginal immune cells were obtained, using absorbent wicks, from 11 normal cycling female monkeys at different stages of the menstrual cycle and from three nursing monkeys (not cycling). Leucocytes, including lymphocytes and monocyte-macrophage cells, were present in the cervicovaginal secretions of healthy cynomolgous primates throughout the three phases of the menstrual cycle. We also found that even if immune cells were constant throughout the menstrual cycle, among the T cell subsets there were differences. CD8+ cells [14.5+/-9% (mean+/-S.D.); range 3-30%] were more numerous compared to the mean number of CD4+ cells [7.3+/-5% (mean+/-S.D.); range 2-15%]. Characterization of the vaginal cells during the nursing period showed that the monocyte-macrophage (CD14+, CD11c+) cells were abundant compared with the low number of both B (CD20+) and T cells (CD2+). Our results show that cytometric analysis by FACS can be used to identify the immune cell populations present at the local level. This technique may provide a useful tool by which the vaginal environment can be studied in order to correlate cell phenotype with immune function.

Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation.

OBJECTIVE: The development of drugs that can be used as topical microbicides is currently recognized as a priority area of research. DESIGN: A preclinical evaluation of the potential effectiveness of TMC120, a non-nucleoside reverse transcriptase inhibitor (NNRTI), as a topical microbicide to prevent vaginal HIV-1 transmission in a humanized severe combined immunodeficient (hu-SCID) mouse model. METHODS: Reconstituted mice received an intravaginal application of a TMC120-containing gel 20 min prior to a non-invasive vaginal challenge with cell-associated HIV. The possible cytotoxic effect of TMC120-containing-gel on lymphocytes was assessed and their in vivo migration was followed using fluorescently labelled human lymphocytes. Systemic infection was monitored by p24 antigen detection in culture supernatant from cocultured intraperitoneal cells using antigen capture enzyme-linked immunosorbent assay test and by the presence of integrated proviral HIV-1 DNA in DNA extracted from spleen cells. In vivo migration of labelled lymphocytes was examined by analysis of cells isolated from regional lymph nodes. RESULTS: In this model, systemic infection was successfully inhibited by the presence of TMC120-containing gel at vaginal level. The in vivo migration of human lymphocytes from the vagina to regional lymph nodes, following the deposition of TMC120-containing gel, excluded the possibility that inhibition of systemic infection was a result of NNRTI toxicity. CONCLUSIONS: Vaginal transmission of HIV was successfully prevented by the application of a gel formulation containing TMC120. This is the first evidence of the in vivo effectiveness of a microbicide preparation containing an NNRTI against cell-associated HIV.