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Abstract
The aim of this study was to use conventional breeding to increase the production in maize of the human monoclonal antibody 2G12, known to have potential therapeutic properties in the prevention of HIV-1 transmission. The recombinant antibody, together with a fluorescent marker, was introduced into two South African high-performing maize elite inbred lines by crossing them with a transgenic maize line that had been transformed with the monoclonal antibody 2G12. The effect of breeding to produce high-expressing recombinant hybrid seed was evaluated by comparing 2G12 production in the different breeding lines with the original maize line. ‘Good production practice standards’ were followed throughout the breeding programme. ‘Conventional drug regulations’ adapted to plant- made pharmaceuticals were also followed, with the seeds being stored in a ‘master seed bank’. The maize hybrid expressed a higher level of the antibody than the recombinant maize elite lines. This plant-derived antibody provides a means of producing a microbicide component that could be used with other HIV-neutralising antibodies as an additional approach to prevent HIV infection.
Highlights
HIV- and AIDS-related infections are possibly the primary cause of death in sub-Saharan Africa and are a leading cause of mortality worldwide, with an estimated two million deaths in 2008 alone
In this study we demonstrate the breeding of these two transgenic maize lines containing 2G12, aimed at the increased production of the 2G12 antibody under greenhouse containment, and confirm the expression of the antibody during all stages of breeding
The transgenic South African elite lines, SSG62B and NSP5120A, containing the stable mAb 2G12 derived from crosses made with primary Hi-II maize transformants that contained 2G12,6 were used in this study for breeding and increased production of 2G12
Summary
HIV- and AIDS-related infections are possibly the primary cause of death in sub-Saharan Africa and are a leading cause of mortality worldwide, with an estimated two million deaths in 2008 alone. The number of people living with HIV/AIDS worldwide was estimated to be 33.4 million, of which 2.7 million were newly infected with HIV.[1] various vaccination strategies have been pursued in an attempt to halt the HIV pandemic, the complex biology of the virus makes it a difficult target for vaccine protection and no effective vaccine has been developed as yet. Cell-free viruses can only be eliminated through binding to neutralising antibodies, whereas cell-associated viruses are mainly eliminated by cell-mediated immune responses. For a vaccine to be effective, it must elicit both types of immune responses . Microbicides, on the other hand, can bypass many of the immunological challenges associated with HIV vaccine development and can be used in the form of topical gels that offer an additional strategy for the prevention of HIV transmission
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