Cost-effective production of a vaginal protein microbicide to prevent HIV transmission

• Published in: Proceedings of the National Academy of Sciences - PNAS 2008-03, Vol.105 (10), p.3727-3732
• Main Authors: Ramessar, Koreen, Rademacher, Thomas, Sack, Markus, Stadlmann, Johannes, Platis, Dimitris, Stiegler, Gabriela, Labrou, Nikos, Altmann, Fritz, Ma, Julian, Stöger, Eva, Capell, Teresa, Christou, Paul
• Format: Article
• Language: English
• Subjects: Administration, Intravaginal; Animals; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - economics; Anti-Infective Agents - immunology; Antibodies; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - isolation & purification; Antiinfectives; Biochemistry; Biological Sciences; CHO cells; Chromatography; Chromatography, Affinity; Corn; Cost-Benefit Analysis; Cricetinae; Cricetulus; Developing countries; Disease prevention; Disease transmission; Drug Administration Routes; Electrophoresis, Polyacrylamide Gel; Embryos; Endosperm; Glycopeptides - chemistry; HIV; HIV Antibodies - biosynthesis; HIV Antibodies - isolation & purification; HIV Antigens - immunology; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - transmission; Human immunodeficiency virus; Humans; LDCs; Mass Spectrometry; Medical treatment; Molecular Weight; Neutralization Tests; Plants, Genetically Modified; Polysaccharides; Polysaccharides - analysis; Proteins; Seeds - metabolism; Staphylococcal Protein A - metabolism; Zea mays - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0708841104

A series of small-molecule microbicides has been developed for vaginal delivery to prevent heterosexual HIV transmission, but results from human clinical trials have been disappointing. Protein-based microbicides, such as HIV-specific monoclonal antibodies, have been considered as an alternative approach. Despite their promising safety profile and efficacy, the major drawback of such molecules is the economy of large-scale production in mammalian cells, the current system of choice. Here, we show that an alternative biomanufacturing platform is now available for one of the most promising anti-HIV antibodies (2G12). Our data show that the HIV-neutralization capability of the antibody is equal to or superior to that of the same antibody produced in CHO cells. We conclude that this protein production system may provide a means to achieve microbicide ingredient manufacture at costs that would allow product introduction and manufacture in the developing world.