A comparative review of serological assays for the detection of rabies virus-specific antibodies

Rabies is a major public health problem with a fatality rate close to 100%, caused by a virus of the Lyssavirus genus, of which rabies virus (RABV) is the prototype. Nonetheless, the complete prevention can be achieved by the induction of neutralizing antibodies by pre- or post-exposure prophylaxis. According to the world health organization (WHO) and World Organization for animal health (OIE), serum titers of rabies virus neutralizing antibodies (RVNA) that are higher or equal to 0.5 international units (IU)/ml indicate adequate immune response after vaccination against rabies. Currently, RFFIT and FAVN are the gold standard tests recommended by both WHO and OIE for detecting and quantitating RVNA in biological samples from individuals or animals previously vaccinated and/or subjects suspected of having been infected by RABV. Although the tests RFFIT and FAVN are efficient, they are time-consuming, labor-intensive manual tests and not cost-effective for routine use. Following the previously mentioned, approaches with alternative methods have been developed to detect RVNA or rabies-specific antibodies in human or animal serum, but with variable success. This work summarizes the advances in the serological assays for the detection of neutralizing antibodies or rabies antibodies and assesses the individual immune status after vaccination against rabies, as well as the mechanisms of RABV neutralization mediated by antibodies. Therefore, the main alternative methods for the determination of RABV or rabies-specific antibodies are exposed, with promising results, besides being easy to execute, of low cost, and representing a possibility of being applied, according to the proposal of each test to the network of Rabies Surveillance Laboratories.