The Role of Neutralizing Antibodies in HIV-1 infection

Human immunodeficiency virus type 1 is a major cause of morbidity and mortality worldwide and there is urgent demand for a protective vaccine. A major goal of vaccine development is the elicitation of antibodies capable of neutralizing diverse strains. In order to achieve this goal it is necessary to understand the dynamic relationship between neutralizing antibodies (NAbs) and HIV-1, in vivo. In humans, HIV-1 rapidly escapes from NAbs, confirming that humoral responses inhibit virus replication. However, neutralizing responses are commonly detected in viraemic patients and the clinical impact of NAbs on HIV-1 control is unclear. To investigate this further, viral load (VL) and NAb activity were assessed longitudinally in patients enrolled into a clinical trial of short-course antiretroviral therapy (ART), administered in early infection. The aims of this study were two-fold: i) to understand the importance of VL in the control of NAb responses and ii) to assess whether NAbs contribute to durable control of VL set-point. A high-throughput pseudovirus neutralization assay was developed, using automated counting procedures to quantify infected TZM-bl reporter cells. The assay was used to assess NAb responses with autologous viruses derived from 22 patients. Seven patients with low VL set-points (