Verification of the rabies virus glycoprotein lower limit of immunogenicity by serological assay

Abstract

Rabies lethality is close to 100% and annually 15 million people receive post-exposure prophylaxis. Testing for vaccines against this zoonosis should ensure its quality. A standardized test by the National Institutes of Health (NIH) test, based on mice immunization and challenge, has been used to determine the potency of vaccine lots. It has several disadvantages, the main one being its significant variability. Several in vitro methods like an Enzyme-linked immunosorbent assay (ELISA) have been proposed based on the quality and quantity of glycoprotein (Glptn) of rabies virus, but may also present limitations such as low sensitivity, instability and imprecision. The estimate of immunogenicity based on neutralizing antibody titer (Nab) evaluated by a serological test (ST) such as the Modified Rapid Fluorescent Focus Inhibition Test (mRFFIT), is not yet efectively applied for human vaccine. Nevertheless, a Nab concentration can be used as a predictor of clinical efficacy of this product in vaccinated humans, so, that can be applied in estimating the vaccine potency. The aim of this study was to verify the lower limit of immunogenicity of the viral Glptn content in mice using mRFFIT. The lower Glptn content by ELISA able to induce Nab response was determined. The results were correlated and demonstrated that ST was able to determine the Glptn immunogenicity lower limit. Our findings suggest that a test based on rabies Nabs may represent an additional alternative for the evaluation of rabies vaccines.