OA30.04
Background: Broadly neutralizing monoclonal antibodies (nAbs) reduce HIV transmission in vitro and in animal models of HIV transmission. However their efficacy in preventing human mucosal transmission of HIV remains unknown. During sexual transmission of HIV, semen is the inoculum and previous studies show that semen contains factors that modulate HIV infection in vitro. We theorize that topically applied nAbs can reduce HIV infection of ectocervical and colonic mucosa in the context of semen.
Methods: nAbs, 4E10, VRC01, PG16 and PG9, were evaluated against HIV-1JR-CSF ex vivo in polarized human ectocervical and colonic tissues. Tissues were treated with nAbs and then inoculated apically with virus in the presence or absence of 50% whole human semen. Viral replication in tissues was monitored by HIVp24 ELISA for up to 21 days post inoculation. Data are presented as the median HIVp24 (pg/mL) and 95% confidence interval of 3–7 tissues from individual donors. ANOVA and post hoc multiple comparison procedures were used to compare nAb and semen treatment groups.
Results: 1.5μM nAbs were required to protect ectocervical tissue compared to 0.03μM nAbs in colonic tissue ex vivo. Treatment of ectocervical tissue with 1.5μM nAbs resulted in protection of 90%, 100%, 80% or 30% of tissues by PG16, PG9, VRC01 and 4E10, respectively. Treatment with 0.03μM PG16, PG9 or VRC01, resulted in protection of 100% of colonic tissues, but only 50% with 4E10. Our combined results show that nAb potency follows the order PG16>PG9>VRC01 >>4E10, consistent between cell-based assays and ex vivo tissue studies. Similar levels of viral inhibition were observed in tissues treated with nAbs in the presence of semen.
Conclusions: Collectively, these data suggest nAbs are effective in the presence of semen and should be considered as a non-chemotherapeutic option for the prevention of HIV. Importantly nAbs could be considered for use in persons already infected with HIV and seeking ways to mitigate transmission to their partners.
