Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent

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When selecting broadly neutralizing antibodies (bnAbs) for clinical application, potency and breadth against free viruses are vital, but additional features may be needed to ensure in vivo efficacy. Considering that HIV-1 can utilize free virus and cell-cell transmission to infect, the efficacy of neutralizing antibodies in vivo may depend on their ability to block both pathways. While breadth and potency of bnAbs against free viruses have been intensely studied, their precise activity during cell-cell spread remains uncertain. Our analysis of the cell-cell neutralization capacity of a large selection of bnAbs against a spectrum of HIV-1 strains revealed that while bnAbs showed an overall decreased activity during cell-cell transmission, losses varied substantially depending on bnAb and virus strain probed. Although bnAbs occasionally retained activity during cell-cell transmission for individual viruses, this ability was rare and generally not associated with a high potency against free virus spread. Notably, neutralization of free virus but not cell-cell transmission was linked with the activity of bnAbs to inhibit prior to CD4 engagement, highlighting the functional differences of the processes. Since no single bnAb combines the entire range of mechanistic features anticipated to support in vivo efficacy, our study adds further evidence that combinations of bnAbs need to be considered for human application.

Vyšlo v časopise: Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004966
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004966

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