Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.
Antimicrob Agents Chemother
; 61(7)2017 07.
Article
em En
| MEDLINE
| ID: mdl-28416548
ABSTRACT
The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (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 underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were 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 of 102 to 103 µg g-1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article