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Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7854-E7862. doi: 10.1073/pnas.1806022115. Epub 2018 Jul 30.

Unexpected synergistic HIV neutralization by a triple microbicide produced in rice endosperm.

Author information

1
Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering, University of Lleida-Agrotecnio Center, 25198 Lleida, Spain.
2
IrsiCaixa AIDS Research Institute, Institut de Recerca Germans Trias i Pujol, Germans Trias i Pujol University Hospital, 08916 Badalona, Barcelona, Spain.
3
Department of Medicine, Imperial College London, W2 1PG London, United Kingdom.
4
TRM Ltd, YO11 9FJ Scarborough, United Kingdom.
5
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.
6
Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.
7
Chair of AIDS and Related Diseases, University of Vic-Central University of Catalonia, 08500 Vic, Barcelona, Spain.
8
Department of Plant Sciences, University of California, Davis, CA 95616; gurdev@khush.org christou@pvcf.udl.es teresa.capell@pvcf.udl.cat.
9
Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering, University of Lleida-Agrotecnio Center, 25198 Lleida, Spain; gurdev@khush.org christou@pvcf.udl.es teresa.capell@pvcf.udl.cat.
10
Catalan Institute for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.

Abstract

The transmission of HIV can be prevented by the application of neutralizing monoclonal antibodies and lectins. Traditional recombinant protein manufacturing platforms lack sufficient capacity and are too expensive for developing countries, which suffer the greatest disease burden. Plants offer an inexpensive and scalable alternative manufacturing platform that can produce multiple components in a single plant, which is important because multiple components are required to avoid the rapid emergence of HIV-1 strains resistant to single microbicides. Furthermore, crude extracts can be used directly for prophylaxis to avoid the massive costs of downstream processing and purification. We investigated whether rice could simultaneously produce three functional HIV-neutralizing proteins (the monoclonal antibody 2G12, and the lectins griffithsin and cyanovirin-N). Preliminary in vitro tests showed that the cocktail of three proteins bound to gp120 and achieved HIV-1 neutralization. Remarkably, when we mixed the components with crude extracts of wild-type rice endosperm, we observed enhanced binding to gp120 in vitro and synergistic neutralization when all three components were present. Extracts of transgenic plants expressing all three proteins also showed enhanced in vitro binding to gp120 and synergistic HIV-1 neutralization. Fractionation of the rice extracts suggested that the enhanced gp120 binding was dependent on rice proteins, primarily the globulin fraction. Therefore, the production of HIV-1 microbicides in rice may not only reduce costs compared to traditional platforms but may also provide functional benefits in terms of microbicidal potency.

KEYWORDS:

HIV combination microbicides; Oryza sativa; gp120 binding; plant-made pharmaceuticals; rice globulins

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