Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120

Abstract

A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming virus and either permanently inactivate it or reduce its infectivity, or it could block receptors on susceptible cells near the sites of transmission. We describe here how vaginal administration of the broadly neutralizing human monoclonal antibody b12 can protect macaques from simian-human immunodeficiency virus (SHIV) infection through the vagina. Only 3 of 12 animals receiving 5 mg b12 vaginally in either saline or a gel and then challenged vaginally (up to 2 h later) with SHIV-162P4 became infected. In contrast, infection occurred in 12 of 13 animals given various control agents under similar conditions. Lower amounts of b12 were less effective, suggesting that protection was dose dependent. These observations support the concept that viral entry inhibitors can help prevent the sexual transmission of HIV-1 to humans.

Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120

“…Topical application of MAb b12 has been shown to protect macaques from infection after vaginal challenge with SHIV, which supports the potential use of antibodies for topical prevention of HIV-1 transmission (82). Further studies are needed to establish whether the identified VHH would have preventive effects in vivo.…”

Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potency

“…Preferred agents for this use inhibit early steps in the HIV cycle, like attachment, fusion, and entry, to prevent integration of the viral genome into chromosomal DNA (53). Successful use of entry inhibitors to block vaginal transmission of HIV in rhesus macaques has been reported (54)(55)(56). It has been shown recently that C34 can completely block HIV infection of Langerhans cells when continuously present before, during, and after exposure of cells to virus, but only partially when the peptide is not present during incubation with virus (51).…”

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

“…Second, passive immunization with 2F5 Abs protected macaques from a mucosal challenge (17,18). Similarly, vaginal application of the gp120-directed b12 Ab was highly effective in protecting monkeys from a vaginal challenge (19). Third, anti-HIV-1 secretory IgA, isolated from mucosal secretions of infected individuals, can block transcytosis of HIV-1 and infection of CD4 ϩ cells ex vivo (20,21) and the neutralization potential of these Abs was greater than the paired IgGs (21).…”