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Biomedical subjects

L Zeitlin

Publications and source records attributed to L Zeitlin.

13 recordsLinked to original sources

Tests of Buffergel for contraception and prevention of sexually transmitted diseases in animal models.

BACKGROUND: BufferGel is a novel spermicidal and microbicidal gel formulated to maintain the natural protective acidity of the vagina by acidifying semen, which otherwise alkalinizes the vagina. GOAL: To test the efficacy of BufferGel for preventing sexually transmitted infections and pregnancy in animal models. STUDY DESIGN: Animals were challenged with pathogens or sperm after pretreatment with both test and control agents, or after no pretreatment, then evaluated for infection or pregnancy using standard methods. RESULTS: BufferGel provided significant contraceptive efficacy in the rabbit, and significant protection against vaginal and rectal transmission of herpes simplex virus type 2 (HSV-2) in the mouse, vaginal transmission of Chlamydia trachomatis in the mouse, and skin transmission of cottontail rabbit papillomavirus in the rabbit. It did not protect against vaginal transmission of Neisseria gonorrhoeae in the mouse. CONCLUSIONS: The protective efficacy of BufferGel in five of the six animal models suggests that this microbicide warrants clinical evaluation for both contraception and disease prevention.

Acrylic Resins↗

Preventing infectious disease with passive immunization.

Antibodies can prevent infectious diseases by providing passive immune protection. Here we review successful clinical trials of passive immunization and consider some of the unique qualities monoclonal antibodies are now beginning to offer for developing methods for passive immunization against a wide range of infectious diseases.

Antibodies, Monoclonal↗

Polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.

PROBLEM: Recent reports indicate high incidence of genital infections, most of which are sexually transmitted. Although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides. METHODS: Formulations at different dilutions were tested in culture systems on standard strains and clinical isolates including some isolates resistant to drugs. The effect on (HSV)-2 and Chlamydia trachomatis was determined in vivo in progestin sensitized mice. The effect on HIV-1 was investigated in two standardized systems. RESULTS: Polyherbal cream inhibited the growth in culture of clinical isolates of Candida albicans, Candida krusei and Candida tropicalis. Both the polyherbal cream and the Praneem polyherbal pessary inhibited urinary tract Escherichia coli (including multidrug resistant strains), and Neisseria gonorrhoeae (including 2 strains resistant to penicillin). Both formulations manifested virucidal activity against HIV-1 at >2 and 50% dilutions (in two different test systems) on contact for 1-2 min. Intravaginal inoculation of the cream and the pessary suspensions before inoculation of the pathogen prevented lesions and vaginal transmission of HSV-2 and C. trachomatis in progestin sensitized mice. CONCLUSIONS: Polyherbal formulations have wide spectrum antibacterial, antifungal and antiviral effect against the tested sexually transmitted pathogens.

Animals↗

Comparison of an anti-HSV-2 monoclonal IgG and its IgA switch variant for topical immunoprotection of the mouse vagina.

An IgG2a monoclonal antibody (Mab) directed against glycoprotein D of herpes simplex virus 2 (HSV-2) was compared with an IgA heavy chain Mab switch variant to investigate the effect of isotype for topical immunoprotection of the murine vagina. The IgA Mab, a mixture of monomeric and polymeric IgA, was indistinguishable from its IgG parent in an in vitro HSV-2 neutralization assay. When these class switched Mabs were delivered to the mouse vagina, we also found no significant difference between the IgG and IgA for preventing vaginal transmission of HSV-2 infection. The implications of these results for active and passive immunization strategies against vaginal transmission of genital herpes infections are discussed.

Administration, Topical↗

A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes.

The ability to produce monoclonal antibodies (Mabs) in plants offers the opportunity for the development of an inexpensive method of mucosal immunoprotection against sexually transmitted diseases. To investigate the suitability of plant-expressed Mabs for vaginal preventive applications, we compared a humanized anti-herpes simplex virus 2 (HSV-2) Mab expressed in mammalian cell culture with the same antibody expressed in soybean. We found these Mabs to be similar in their stability in human semen and cervical mucus over 24 h, their ability to diffuse in human cervical mucus, and their efficacy for prevention of vaginal HSV-2 infection in the mouse.

Animals↗

Tests of vaginal microbicides in the mouse genital herpes model.

Microbicide candidates were selected that have demonstrated activity against sperm or sexually transmitted disease pathogens in vitro, and the efficacy of these agents for preventing vaginal transmission of genital herpes infection was evaluated in the progestin-treated mouse. Each agent was delivered to the vaginas of mice approximately 20 sec prior to delivering a highly infectious herpes simplex virus-2 inoculum. The following agents provided significant protection: anti-HSV monoclonal antibodies III-174 and HSV8, modified bovine beta-lactoglobulin (beta-69), carrageenan, concanavalin A, chlorhexidine, dextran sulfate (average molecular weight 8,000 and 500,000), fucoidan, neem, nonoxynol-9, polystyrene sulfonate, and povidone-iodine. Two agents, gramicidin and heparan sulfate, though highly effective in vitro, were not protective in vivo at the doses tested.

Animals↗

Topically applied human recombinant monoclonal IgG1 antibody and its Fab and F(ab')2 fragments protect mice from vaginal transmission of HSV-2.

A recombinant human anti-herpes simplex virus monoclonal IgG1, antibody and the corresponding Fab and F(ab')2 fragments were tested for efficacy in preventing vaginal transmission of HSV-2 infection in a well-established mouse model for genital herpes. IgG1, Fab, and F(ab')2 were approximately equally protective; vaginal delivery of 1-5 ng provided approximately 50% protection, and vaginal delivery of 400 ng completely protected mice from genital herpes infection (P < 0.001). These results suggest that topical applications of human monoclonal antibodies may be useful in developing new methods for preventing sexually transmitted disease.

Administration, Intravaginal↗

Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes.

Current methods for sexually transmitted diseases (STD) prophylaxis, which can be disruptive and inconvenient, must be used before each act of sexual intercourse, so a method that provides protection over the course of many acts is desirable. We used a mouse model of vaginally-transmitted herpes simplex virus 2 (HSV-2) infection to test polymeric controlled-release devices for sustained passive immunoprotection. Vaginal disks were prepared by dispersing a monoclonal antibody to HSV-2 (III-174) within a matrix of poly(ethylene-co-vinyl acetate); these disks released 2 to 40 micrograms/day of antibody into buffered water. When disks were placed in the vagina, large amounts of III-174 (5 to 3,000 ng) were recovered from the vaginal fluid over the next 8 days. Mice were vaginally challenged with 10 ID50 of HSV-2 either 3 or 7 days after disk placement; no mice receiving III-174 disks became infected, while 65% of control mice receiving identical disks with nonspecific IgG did. Controlled-release disks with III-174 provided significant protection against HSV-2 infection (p < 0.005). This new technology for long-term STD prophylaxis should increase user compliance, a factor limiting the efficacy of current methods.

Administration, Intravaginal↗

Residence half-life of IgG administered topically to the mouse vagina.

Antibodies delivered directly to the vagina can provide passive immunoprotection against pregnancy and sexually transmitted disease. The duration of protection is limited by the residence time of the antibodies in the vagina; to our knowledge such residence times have not been reported. We investigated the time-course of disappearance of IgG delivered to the mouse vagina using three different methods to monitor the amount of administered IgG remaining in the vagina: gamma counting of 125I-IgG, viral neutralization of unlabeled monoclonal anti-herpes virus IgG2a, and ELISA of biotinylated IgG. The test IgG was delivered to the vagina in saline and recovered by lavage. All three methods yielded similar results, suggesting that the residence half-life is not significantly affected by the volume administered, phase of the estrous cycle, or labeling of IgG. In awake mice, a significant fraction of IgG disappeared with a relatively short half-life, (t1/2)alpha, of 0.7 +/- 0.1 h; but this rapid (alpha phase) decrease did not occur in anesthetized mice, suggesting that the movements of awake mice expel some of the test IgG-saline solution from the vagina. Over the next 25 h, the test IgG disappeared with a residence half-life, (t1/2)beta, of 5 +/- 2 h. We believe this slow elimination of IgG may depend on the rate that mucus secretions are shed from the vagina.

Administration, Topical↗

Passive immunization of the vagina protects mice against vaginal transmission of genital herpes infections.

Vaginal application of human herpes simplex virus (HSV) antiserum, complement-inactivated antiserum, or IgG purified from antiserum protected mice (P < .001, P < .001, and P < .01, respectively) from visible signs of genital HSV-2 infection after subsequent vaginal inoculation with HSV-2 (10 ID50). Vaginal application of an anti-HSV-2 monoclonal antibody (MAb III-174) also protected mice against infection. This MAb, a neutralizing mouse IgG2A against glycoprotein D, prevented infection as determined by viral shedding from the vagina (P < .05), blocked 50% of visible signs of genital herpes infection at a vaginal dose of approximately 10 ng, and blocked 100% of visible signs of infection at a vaginal dose of 1 microgram (P < .001). These results suggest that vaginal applications of anti-HSV antibodies may help prevent sexual transmission of genital herpes infection.

Animals↗

Nonoxynol-9 protects mice against vaginal transmission of genital herpes infections.

A vaginal application of a commercially available contraceptive jelly containing nonoxynol-9 (N9) prevented vaginal transmission of herpes simplex virus type 2 (HSV-2) infections in the mouse. When N9 jelly was delivered to the vagina with the virus inoculum, 20 s before inoculum, or 5 min before inoculum, mice were completely protected from visible infection (P < .001). Protection lasted for at least 30 min (P < .03), and significant protection occurred even when the N9 jelly was delivered 15 min after the HSV-2 inoculum (P < .05). These results are consistent with results of studies using N9 products in other animal models and suggest that N9-based contraceptive products can provide significant protection against vaginal transmission of enveloped virus infections in animals.

Animals↗

Using monoclonal antibodies to prevent mucosal transmission of epidemic infectious diseases.

Passive immunization with antibodies has been shown to prevent a wide variety of diseases. Recent advances in monoclonal antibody technology are enabling the development of new methods for passive immunization of mucosal surfaces. Human monoclonal antibodies, produced rapidly, inexpensively, and in large quantities, may help prevent respiratory, diarrheal, and sexually transmitted diseases on a public health scale.

Animals↗