Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model [PublishAheadOfPrint]

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known HIV-1 isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other under-developed regions may be limited by the high cost and limited manufacturing capacity of conventionally produced antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01-N over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs was evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range 10² — 10³ μg g^-1 that were correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that VRC01-N pod-IVRs are a promising candidate topical microbicide against HIV-1 infection and merit further pre-clinical evaluation.

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