Gaudinski MR, Houser KV, Doria-Rose NA, et al. - Researchers conducted this phase 1, open-label, dose-escalation clinical trial in order to ascertain the safety, tolerability, and pharmacokinetic profile of the broadly neutralising monoclonal antibody VRC07-523LS, an engineered variant of VRC01 that targets the CD4 binding site of the HIV-1 envelope protein, in healthy adults. This trial was done at the National Institutes of Health Clinical Center in Bethesda, MD, USA, and included 26 individuals (HIV-1-negative adults aged 18–50 years) from the greater Washington, DC, area by IRB-approved written and electronic media. Based on their self-selection, participants were included in seven open groups: a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07-523LS was provided to four groups, a single 5 mg/kg subcutaneous dose was provided to one group and three doses of either 20 mg/kg intravenous VRC07-523LS, or 5 mg/kg subcutaneous VRC07-523LS at 12-week intervals were provided to two groups. VRC07-523LS was identified as safe and was well-tolerated among the participants. Based on the outcomes, VRC07-523LS is supported as a strong and practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. In addition, this trial shows the possible safety of an HIV-1 broadly neutralising monoclonal antibody, engineered for improved pharmacokinetic and neutralisation properties, for clinical use.