Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.

Therapeutic and Prophylactic Potential of FMD Virus-specific Polyvalent Immunoglobulins during an FMD Outbreak in Cattle

Foot and mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals worldwide. In the present study the therapeutic and prophylactic potential of polyclonal, polyvalent FMD virus-specific bovine antibodies has been investigated as a possible approach for rapid control, lessening of the severity of clinical signs and prophylactic protection of susceptible animals during FMD outbreaks. The prepared FMD virus-specific polyvalent immunoglobulins were concentrated, purified, filter sterilized (0.22nm) and its titer against the FMD virus serotypes, A, O and SAT2, was adjusted to 2.15, 2.25 and 2.10 log10 TCID50/ml, respectively. In an experimental FMDV induced infection, the immunoglobulin therapy was given 4 days post experimental infection. The effect of different doses of immunoglobulins (4, 6 and 8ml) the severity of the clinical signs, healing of lesions and virus shedding was determined. A dose of 8 ml (2.0 log10 TCID50/ml) of the prepared FMD virus-specific antibodies proved highly effective in reducing the severity of the clinical signs and inducing recovery within 48 - 96hrs post therapy, as compared with the control non-treated infected calves. A dose related recovery rate was recorded. Field trial was conducted and evaluated during the FMD outbreak in Egypt during 2016/2017. Significant reduction of the morbidity of the disease and 100% reduction of mortality were recorded. The prepared FMD virus-specific bovine polyvalent antibodies proved to be a drug of choice during FMD outbreaks protecting susceptible animals and inducing rapid recovery of diseased one associated with reducing clinical signs severity and reducing virus shedding.