PubMed Health⌕ Search

PubMed · 10667178

Thinking about vaginal microbicide testing.

Abstract

A vaginal microbicide could slow the spread of HIV. To date, volunteers in placebo-controlled trials of candidate microbicides have been counseled to use condoms. This does not reduce the number of volunteers exposed to possible risk, but it shifts the allotment of risk from those conducting the trial to those women who may be least able to make autonomous decisions. Alternative ways of meeting the obligation to offer volunteers active benefits are explored. Counseling the use of condoms prolongs clinical trials and could cause tens of thousands of otherwise avoidable deaths.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M Potts. 2000. Thinking about vaginal microbicide testing.. https://doi.org/10.2105/ajph.90.2.188

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Vaginal mucosa serves as an inductive site for tolerance.

These data demonstrate that tolerance can be induced by vaginal Ag exposure. In these experiments, mice were given vaginal agarose gel suppositories containing either 5 mg OVA or saline for 6 h. Mice were given suppositories either during the estrous (estrogen dominant) or diestrous (progesterone dominant) stage of the estrous cycle. Mice were restrained during the inoculation period to prevent orovaginal transmission of the Ag. After 1 wk, mice were immunized s. c. with OVA in CFA. After 3 wk, mice were tested for delayed-type hypersensitivity responses by measuring footpad swelling and measuring in vitro proliferation of lymphocytes to Ag. Using ELISA, the magnitude of the serum Ab response was also measured. In some mice, FITC conjugated to OVA was used to track the dissemination of the protein into the systemic tissues. The magnitude of footpad swelling was significantly reduced in mice receiving OVA-containing suppositories during estrus compared with mice receiving saline suppositories. Concomitant decreases in the Ag-specific proliferative response were also observed in lymph node lymphocytes and splenocytes. Conversely, mice inoculated during diestrus did not show a decreased response to Ag by either footpad response or in vitro proliferation. Serum Ab titers in the estrus-inoculated mice did not decrease significantly. These data demonstrate that the reproductive tract can be an inductive site for mucosally induced tolerance. However, unlike other mucosal sites such as the lung and gastrointestinal tract, reproductive tract tolerance induction is hormonally regulated.

Administration, Intravaginal↗

Induction of an HPV 6bL1-specific mucosal IgA response by DNA immunization.

Human papillomavirus (HPV) plays a crucial role in the development of human anogenital dysplasia. To prevent infection, it is important to induce an HPV-specific mucosal immune response. We investigated whether DNA vaccination would induce an intravaginal mucosal antibody response against HPV 6bL1. New Zealand White rabbits were immunized with an HPV 6bL1 DNA vaccine by one of the three routes: muscular, vaginal, or rectal. We found that vaginal immunization of rabbits with HPV 6bL1 DNA induced 6bL1 virus-like particle-specific lgA antibodies in vaginal secretions. They were detectable until at least 14 weeks after the first immunization. The antibodies also showed neutralizing activity in a hemagglutination inhibition assay. No mucosal immune response was detected in vaginal secretions of rabbits immunized intramuscularly or intrarectally. Our data suggest that vaginal immunization with HPV 6bL1 DNA induces long-lasting IgA responses with neutralizing activity in vaginal secretions of rabbits.

Administration, Intravaginal↗

High-performance liquid chromatographic determination of 17beta-estradiol and 17beta-estradiol-3-acetate solubilities and diffusion coefficents in silicone elastromeric intravaginal rings.

A rapid, sensitive reversed-phase high-performance liquid chromatographic method has been developed for the determination of in vitro release of 17beta-estradiol and its ester prodrug, 17beta-estradiol-3-acetate, from silicone intravaginal rings. Partial hydrolysis of the acetate under the aqueous conditions provided by the 1% benzalkonium chloride release medium necessitates its conversion to 17beta-estradiol prior to HPLC analysis. Both steroid peaks have been fully resolved from the benzalkonium chloride peaks by the reported chromatographic method, which employs a C18 bonded reversed-phase column, an acetonitrile-water (50:50, v/v) mobile phase and a UV detection wavelength of 281 nm. The peak area versus 17beta-estradiol concentration was found to be linear over the range of 0.0137-1347 microkg ml(-1). The HPLC method has also been used to determine the silicone solubilities and diffusion coefficients of the two related steroids. The almost 100-fold increase in 17beta-estradiol-3-acetate release from the silicone core-type intravaginal rings compared to 17beta-estradiol is shown to be due to a 60-fold increase in silicone solubility and a one and a half-fold increase in diffusitivity. The results demonstrate that an effective estrogen replacement therapy dose of 17beta-estradiol may be administered from a silicone intravaginal reservoir device containing the labile 17beta-estradiol-3-acetate prodrug.

Administration, Intravaginal↗