Neutralization of Yellow Fever Virus Studied Using Monoclonal and Polyclonal Antibodies

Abstract

Monoclonal and polyclonal antibodies with known specificity for either the 54K envelope glycoprotein or the 48K non-structural glycoprotein of yellow fever (YF) virus-infected cells were studied in plaque reduction neutralization test. Viruses employed in the tests comprised wild-type and vaccine strains of YF and a selection of other flaviviruses. Of 17 monoclonal antibodies examined, six of the 54k-specific antibodies neutralized at least one YF preparation. Both vaccine and wid-type YF viruses varied in their susceptibility to neutralization and there were also differences between individual 17D vaccine strains. The monoclonal antibodies produced a range of titres with the different viruses, the most potent, 864, leaving no non-neutralizable fraction. Addition of anti-globulin, complement or other antibodies did not affect the results. YF-neutralizing antibodies which bound to other flaviviruses did not necessarily neutralize them; hence, neutralization could be defined as either homotypic, heterotypic or both homotypic and heterotypic. A polyclonal antiserum and a broadly reacting monoclonal antibody produced almost identical neutralization results in test with wild-type YF viruses. In contrast, the polyclonal antiserum produced higher titres with vaccine strains of YF. In mouse passive protection experiments on the other hand, the monoclonal antibody did not differentiate between these viruses.