Neutralizing and Non-Neutralizing HIV-Specific Antibodies Hinder the Movement of Virus in Fresh Human Cervical Mucus

During sexual transmission, HIV must overcome mucosal barriers to reach underlying target cells. The epithelial barrier function of the female reproductive tract is further enhanced by a protective layer of cervical mucus (CM). It is believed that antibodies associated with mucus barriers of the gut can have antimicrobial activity. We explored the possible role that antibodies which can bind to virions might alter particle transport through mucus. To characterize the effects of HIV-specific antibodies on viral diffusion in CM, we utilized two red and green fluorescently tagged HIV types: wildtype enveloped virus (WT-Gag-mCherry) and HIV devoid of envelope proteins, ([INCREMENT]Env-Gag-GFP) which allows for simultaneous visualization of both virus types in CM. For our assay, both virus types were mixed at equal concentrations and either added directly to CM or incubated with HIV-specific antibodies prior to being added to CM. We found that using anti-MHC class I antibodies, which bind epitopes found on WT and [INCREMENT]Env virus, decrease the movement of both virus types. Neutralizing and non-neutralizing anti-gp41 and anti-gp120 antibodies specifically impaired the mobility of WT virus when compared to [INCREMENT]Env virus or when compared to virions that received no antibody treatment. We observed greater inhibition of HIV transport in CM with multimeric anti-Env antibodies when compared to monomeric antibodies. Our studies reveal that virus binding antibodies can slow the transport of HIV within the mucus coating of the female reproductive tract. This suggests that a vaccine that generates broadly binding antibodies could potentially prevent viral interactions with target cells thus offering protection against productive infection.