Rapid loss of activity but not serum concentration in a passive infusion clinical trial of an HIV neutralizing antibody

Monoclonal antibodies (mAbs) are a major class of drugs for treatment and prevention of disease. In early clinical trials, the pharmacokinetics (pK) of mAbs are usually assessed by measuring mAb concentration in serum. However, it is not a given that the mAbs will retain full functionality over time, emphasizing the need for integrated PK and functional assessments. In a re-analysis of data from the CAPRISA 012B trial, a previously published phase 1 study evaluating mAbs CAP256V2LS and VRC07-523LS in HIV-negative women, we report an unexpected disconnect between serum bNAb concentrations and HIV neutralization activity of CAP256V2LS, with implications for ongoing assessment of passive immunization trials.