Monoclonal antibodies(mAbs)show promise as multipurpose prevention technology.The MB66 intravaginal film contains 10 mg each of anti-HIV(VRC01) and anti-HSV(HSV8) mAbs to provide protection against two incurable viral infections.
The active film or vehicle control film was randomly assigned at a 1:1 ratio to 29 healthy sexually abstinent women who were instructed to insert 1 film daily for 7 days.Visits and clinical sampling occurred predose at 1, 4, 24 hrs after the 1st dose and 24 hrs, 6-10 days after the 7th dose.Cervicovaginal lavage samples (CVLs) were assayed by Luminex for 16 cytokines that have been associated with HIV transmission,by TZM-bl assay for HIV neutralization[strains:Q23-1 (R5 clade A), BaL (R5 clade B),and LAI (X4 clade B)],and by Plaque Reduction NeutralizationTest for HSV-2 neutralization [HSV-2 strain G].CVLs and TearFlo samples(4 vaginal sites)were assessed by ELISA for VRC01 and HSV8 mAb concentrations.
There were 45 AEs;19 were deemed related to study product, but were balanced between active and placebo film (p’s=1.0).There were no serious AEs(SAEs) and no significant differences in levels of proinflammatory cytokines, Nugent Scores,vaginal pH between Active and Placebo film groups(p’s>0.10).Acceptability and willingness to use the product were judged to be high by post-use ACASI questionnaire.Concentrations of VRC01 and HSV8 increased significantly in vaginal secretions following insertion of Active film.Antibody levels in TearFlo samples peaked at 1 hr post-dosing (median:35 µg/mL) but remained significantly elevated at 24 hours post 1st and 7th film. (median: ~ 1.8 µg/mL). In light of an estimated dilution factor of 35 for the TearFlo samples,the extrapolated VRC01 concentrations range from 63-1,225 times IC50 for VRC01(~1 µg/mL).CVLs from the active film group, collected 24 hr after 1st film and 7th films,significantly neutralized all 3 HIV strains and HSV-2.
Repeated doses of MB66 film was safe and tolerated.Significant HIV-1 and HSV-2 neutralization (ex vivo) was observed at 24 hrs,7 films. Antibody levels in vagina had concentrations consistent with protection for up to 24 hrs.