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

被引:122
作者
Ramessar, Koreen [1 ]
Rademacher, Thomas [2 ]
Sack, Markus [2 ]
Stadlmann, Johannes [3 ]
Platis, Dimitris [4 ]
Stiegler, Gabriela [5 ]
Labrou, Nikos [4 ]
Altmann, Fritz [3 ]
Ma, Julian [6 ]
Stoeger, Eva [2 ]
Capell, Teresa [1 ,6 ]
Christou, Paul [1 ,7 ]
机构
[1] Univ Lleida, Dept Prod Vegetali & Ciencia Forestal, Lleida 25198, Spain
[2] Rhein Westfal TH Aachen, Inst Mol Biotechnol, D-52074 Aachen, Germany
[3] Univ Nat Resources & Appl Life Sci, Glycobiol Div, Dept Chem, A-1190 Vienna, Austria
[4] Agr Univ Athens, Dept Agr Biotechnol, Athens 11855, Greece
[5] Polymun Sci, A-1190 Vienna, Austria
[6] St Georges Univ London, London SW17 0RE, England
[7] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain
关键词
D O I
10.1073/pnas.0708841104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3727 / 3732
页数:6
相关论文
共 50 条
[1]   Widely separated multiple transgene integration sites in wheat chromosomes are brought together at interphase [J].
Abranches, R ;
Santos, AP ;
Wegel, E ;
Williams, S ;
Castilho, A ;
Christou, P ;
Shaw, P ;
Stoger, E .
PLANT JOURNAL, 2000, 24 (06) :713-723
[2]   Galactose-extended glycans of antibodies produced by transgenic plants [J].
Bakker, H ;
Bardor, M ;
Molthoff, JW ;
Gomord, V ;
Elbers, I ;
Stevens, LH ;
Jordi, W ;
Lommen, A ;
Faye, L ;
Lerouge, P ;
Bosch, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2899-2904
[3]   EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY [J].
BURTON, DR ;
PYATI, J ;
KODURI, R ;
SHARP, SJ ;
THORNTON, GB ;
PARREN, PWHI ;
SAWYER, LSW ;
HENDRY, RM ;
DUNLOP, N ;
NARA, PL ;
LAMACCHIA, M ;
GARRATTY, E ;
STIEHM, ER ;
BRYSON, YJ ;
CAO, YZ ;
MOORE, JP ;
HO, DD ;
BARBAS, CF .
SCIENCE, 1994, 266 (5187) :1024-1027
[4]   Industrial choices for protein production by large-scale cell culture [J].
Chu, L ;
Robinson, DK .
CURRENT OPINION IN BIOTECHNOLOGY, 2001, 12 (02) :180-187
[5]   NEUTRALIZATION OF DIVERGENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS AND PRIMARY ISOLATES BY IAM-41-2F5, AN ANTI-GP41 HUMAN MONOCLONAL-ANTIBODY [J].
CONLEY, AJ ;
KESSLER, JA ;
BOOTS, LJ ;
TUNG, JS ;
ARNOLD, BA ;
KELLER, PM ;
SHAW, AR ;
EMINI, EA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :3348-3352
[6]   The design of drugs for HIV and HCV [J].
De Clercq, Erik .
NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (12) :1001-1018
[7]   Endosperm-specific co-expression of recombinant soybean ferritin and Aspergillus phytase in maize results in significant increases in the levels of bioavailable iron [J].
Drakakaki, G ;
Marcel, S ;
Glahn, RP ;
Lund, EK ;
Pariagh, S ;
Fischer, R ;
Christou, P ;
Stoger, E .
PLANT MOLECULAR BIOLOGY, 2005, 59 (06) :869-880
[8]   Plant-based production of biopharmaceuticals [J].
Fischer, R ;
Stoger, E ;
Schillberg, S ;
Christou, P ;
Twyman, RM .
CURRENT OPINION IN PLANT BIOLOGY, 2004, 7 (02) :152-158
[9]   Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: an overview [J].
Floss, Doreen Manuela ;
Falkenburg, Dieter ;
Conrad, Udo .
TRANSGENIC RESEARCH, 2007, 16 (03) :315-332
[10]   Neutralization of the human immunodeficiency virus type 1 primary isolate JR-FL by human monoclonal antibodies correlates with antibody binding to the oligomeric form of the envelope glycoprotein complex [J].
Fouts, TR ;
Binley, JM ;
Trkola, A ;
Robinson, JE ;
Moore, JP .
JOURNAL OF VIROLOGY, 1997, 71 (04) :2779-2785