Monoclonal antibodies (mAbs) show promise as multipurpose prevention technology because their specificity and diversity enable broad-spectrum activity. The MB66 product comprises a combination of anti-HIV and anti-HSV mAbs, produced in Nicotiana (N), to provide protection against two incurable viral infections with high and synergistic morbidity. We sought to assess in women the safety and antiviral effects (ex vivo) of MB66 film antibodies when delivered vaginally.
The MB66 film contains 10 mg of VRC01-N (anti-HIV-1 mAb) and 10 mg of HSV8-N (anti-HSV-2 mAb). Eight healthy and sexually abstinent women without evidence of genital tract infections were enrolled. A study clinician manually inserted the MB66 film in the clinic. Visits and clinical sampling occurred at baseline, 1, 4, 24 hrs and 6-10 days post dose. Adverse events were documented based on DAIDS adverse event grading. Aliquots of cervicovaginal lavage samples (CVLs) were assayed by Luminex for 15 cytokines that have been associated with HIV transmission, by TZM-bl assay for HIV neutralization [HIV strains: Q23-17 (R5 clade A, transmitter/founder strain), BaL (R5 clade B), and LAI (X4 clade B)], and by Plaque Reduction Neutralization Test for HSV-2 neutralization [HSV-2 strain G].
There were four reported adverse events: Grade 1 (cramping, spotting and rash on chest) and Grade 2 (vaginal itching). Only the spotting was deemed related to product. Levels of proinflammatory or other cytokines were not significantly increased in CVLs from the 24hr and 6-10 day time points compared to baseline. Significant HIV neutralization was observed for Visit 3 CVLs (24 hrs after film insertion) for all 3 HIV strains and for HSV-2. Neutralizing activity in Visit 4 CVLs (6-10 days post film use) was not significantly different from Visit 1 (baseline) CVLs.
Single dose vaginal application of MB66 film was safe and well-tolerated. Significant HIV-1 and HSV-2 neutralization (ex vivo) was observed at 24 hours post-film insertion.