prevent sexually transmitted HIV,

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals that directly target viral entry and avert infection at mucosal surfaces. However, most promising antiretroviral entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, O’Keefe and colleagues report a manufacturing breakthrough for griffithsin, one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing griffithsin (GRFT). Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, the authors also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes.

Editors’ note: This study reports an exciting new development on the microbicide front - using Nicotiana benthamiana, a close relative of Nicotiana tobaccum (tobacco), and a tobacco mosaic virus vector to produce large quantities of a red algal protein, griffithsin, that is both directly virucidal to HIV and blocks cell-to-cell HIV transmission. This HIV entry inhibitor is unlikely to be absorbed systemically when applied topically and the vector used to produce it here is already manufacturing proteins used in clinical trials. Critically, griffithsin does not induce any of the proinflammatory cytokines known to recruit HIV target cells and promote HIV replication. These findings provide support in favour of griffithsin now advancing to human trials.