Antibody detection plays a pivotal role in the diagnosis of pathogens and monitoring the success of vaccine immunization. However, current serology techniques require multiple, time-consuming washing and incubation steps, which limit their applicability in point-of-care (POC) diagnostics and high-throughput assays. We developed here a nucleic acid nanoswitch platform able to instantaneously measure immunoglobulins of type G and E (IgG and IgE) levels directly in blood serum and other bodily fluids. The system couples the advantages of target binding induced colocalization and nucleic acid conformational-change nanoswitches. Due to the modular nature of the recognition platform, the method can potentially be applied to the detection of any antibody for which an antigen can be conjugated to a nucleic acid strand. In this work we show the sensitive, fast and cost-effective detection of four different antibodies and demonstrate the possible use of this approach for the monitoring of antibody levels in HIV+ patients immunized with AT20 therapeutic vaccine.