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In the current issue of the Journal, Bettina Sallé and coworkers [1] describe infection of female macaques after atraumatic instillation of simian immunodeficiency virus (SIV)-infected cells into the vaginal cavity. This new SIV infection model represents a significant advance for human immunodeficiency virus (HIV) transmission and prevention research. Whereas HIV-infected cells in genital secretions (“Trojan Horse leukocytes”) may play an important role in the sexual transmission of HIV [2], they have been largely overlooked in recent studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candidates. Current preclinical assays for the development of HIV prevention drugs and vaccines predominately use cell-free viral stocks, and the most popular macaque vaginal SIV transmission models used for vaccine and microbicide preclinical efficacy trials require superphysiological doses of cell-free virus and treatment with high doses of progestins to achieve high infection rates [3]. Because the molecular events underlying cell-associated transmission differ from those involved in cell-free virus transmission, many of the current vaccine and microbicide candidates shown to be effective against cell-free virus may not protect against cell-associated viral transmission. The failure of several recent vaccine and microbicide clinical trials to prevent HIV transmission [4] may be due, in part, to this oversight.

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Editorial Commentary
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