Antibody response to gp E of tick-borne encephalitis virus: comparison between natural infection and vaccination breakdown

Human sera obtained after tick-borne encephalitis (TBE) without prior vaccination were compared with sera from patients after a vaccination breakdown. Most sera previously shown to have high titers of IgG and IgM against TBE virus as detected in the ELISA and hemagglutination inhibition (HI) tests also reacted in Western blot with TBE virus E protein which is involved in virus neutralization. The serum of a patient with a vaccination breakdown, however, reacted only very weakly with the E protein in the Western blot in spite of a high amount of antibodies detectable in ELISA. Using SDS-denaturated virus as an antigen in ELISA (imitating the blotting condition), this serum revealed a significant reduction in its reactivity with denatured virus compared to the control sera. This indicates that the patient had an insufficient immune response against certain denaturation resistant epitopes which might contribute to development of disease despite vaccination. The analysis of the immune response of human sera at the epitope level revealed a characteristic "fingerprint" for each serum reflecting the genetic control of the production of antibody populations against different antigenic determinants.