CORRELATION BETWEEN ELISA, HEMAGGLUTINATION INHIBITION, AND NEUTRALIZATION TESTS AFTER VACCINATION AGAINST TICK-BORNE ENCEPHALITIS

The significance of IgG antibody levels determined by a binding assay (ELISA) was investigated as a surrogate marker for the presence of neu tralizing and hemagglutination inhibiting antibodies in sera from indi viduals vaccinated against tick-borne encephalitis (TBE). To assess th e extent of interference by flavivirus crossreactive antibodies, sera from persons with a proven or suspected history of other flavivirus in fections and/or vaccinations were also examined. An excellent and high ly significant correlation was found between ELISA IgG units and the a ntibody liters obtained by the hemagglutination inhibition (HI) as wel l as by the neutralization test (NT), provided that there was no other exposure to flavivirus antigens except TEE vaccination. Yellow fever vaccination and/or dengue virus infections induced significant levels of antibodies reactive in the TBE ELISA and HI test, which did not exh ibit, however, neutralizing activity against TEE virus. The phenomenon and problem of ''original antigenic sin'' was demonstrated in a TEE v accinee with a history of previous flavivirus infections. TEE vaccinat ion first induced a booster reaction resulting in a rise in the level of cross-reactive antibodies only, whereas TEE virus-neutralizing anti bodies became detectable only after the third vaccination. It is concl uded that the level of IgG antibodies determined by ELISA is a good ma rker for predicting the presence of neutralizing antibodies after TEE vaccination, but only in the absence of flavivirus cross-reactive anti bodies. Otherwise, a neutralization assay is necessary for assessing i mmunity. (C) 1996 Wiley-Liss, Inc.