Llama Antibody Fragments Have Good Potential for Application as HIV Type 1 Topical Microbicides
| Autor: | Andrea Gorlani, H. De Haard, P. van der Bijl, Karl Malcolm, Joachim Brouwers, Theo Verrips, Christopher F McConville, Anna Forsman Quigley, Robin A. Weiss, Patrick Augustijns |
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| Rok vydání: | 2012 |
| Předmět: |
Immunology
Antibody Affinity Human immunodeficiency virus (HIV) Enzyme-Linked Immunosorbent Assay Saccharomyces cerevisiae Biology medicine.disease_cause Antibody fragments Microbiology Virology Microbicide HIV Seropositivity medicine Animals Humans Contraceptive Devices Female Hiv seropositivity Controlled release Bioavailability Topical microbicides Infectious Diseases Anti-Infective Agents Local HIV-1 Vaginal Creams Foams and Jellies Female Immunoglobulin Heavy Chains Camelids New World Ex vivo |
| Zdroj: | AIDS Research and Human Retroviruses. 28:198-205 |
| ISSN: | 1931-8405 0889-2229 |
| Popis: | There is an urgent global need for preventive strategies against HIV-1 infections. Llama heavy-chain antibody fragments (VHH) are a class of molecules recently described as potent cross-clade HIV-1 entry inhibitors. We studied the potential of a VHH-based microbicide in an application-oriented fashion. We show that VHH can be inexpensively produced in high amounts in the GRAS organism Saccharomyces cerevisiae, resulting in a very pure and endotoxin free product. VHH are very stable under conditions they might encounter during transport, storage, or use by women. We developed active formulations of VHH in aqueous gel and compressed and lyophilized tablets for controlled release from an intravaginal device. The release profile of the VHH from, e.g., a vaginal ring suggests sufficient bioavailability and protective concentration of the molecule at the mucosal site at the moment of the infection. The ex vivo penetration kinetics through human tissues show that the VHH diffuse into the mucosal layer and open the possibility to create a second defense layer either by blocking the HIV receptor binding sites or by blocking the receptors of immune cells in the mucosa. In conclusion, our data show that VHH have a high potential for HIV-1 microbicide application because of their low production costs, their high stability, and their favorable release and tissue penetration properties. |
| Databáze: | OpenAIRE |
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