cientists recently have focused on the development of a microbicide to reduce or prevent the sexual transmission of HIV. A microbicide in the form of a cream or a gel could be applied topically prior to intercourse to the vagina or rectum of a person at risk of sexually contracting HIV, lowering the chances of transmission. Despite all the efforts and the urgent need for an effective microbicide against HIV, none is currently available.
In the March issue of Nature Medicine, a group led by John P. Moore at the Department of Microbiology and Immunology at Cornell University, New York demonstrated that a microbicide containing the human monoclonal antibody b12 could effectively protect monkeys against the simian-human immunodeficiency virus (SHIV). The b12 antibody binds to the gp120 protein in the virus.
Using a SHIV derived from a subtype-B primary isolate that uses CCR5 as co-receptor (SHIV-162P4 subtype), the group showed that only 3 of 12 animals receiving 5 mg of b12 vaginally became infected after challenge. The female monkeys received an inoculum that contained 8.6 x 107 RNA copies of the virus. This number of copies corresponds to approximately 2 ng of the gp120 protein. To gain maximum protection, a large molar excess of b12 (>106 fold) was required.
The authors recognize that, in practice, to develop a highly effective microbicide against HIV, it would be necessary to combine it with other neutralizing antibodies such as 2G12, 2F5, 4E10 and Z13, because b12 is not a pan-reactive antibody.
Most antibodies currently in development are produced in cultured rodent cells, a technology that is very expensive. This high cost has been the main obstacle to the large-scale production of recombinant monoclonal antibodies. A practical solution, the authors suggest, would be the use of an alternative technology known as ‘plantibodies’ [PubMed] first described in the late 1980s and which has been gaining ground lately. Shortly, plantibodies are plant-derived therapeutic recombinant antibodies which can be produced economically in a large scale. Indeed, Epicyte Pharmaceutical Inc., a company based in San Diego, California, recently announced the development of the first greenhouse plant lines that produce an antibody that binds to HIV Env proteins. This technology could indeed become a cost-effective and safe alternative for the production of monoclonal antibodies against HIV for microbicides.
*Associate Editor, AIDScience
