Use of a monoclonal antibody specific for wild-type yellow fever virus to identify a wild-type antigenic variant in 17D vaccine pools

Abstract

Monoclonal antibodies (MAbs) against the Asibi wild-type strain of yellow fever (YF) virus were prepared and characterized. One of the MAbs (designated MAb 117) was shown, by cross-immunofluorescence tests with flaviviruses, to be specific for wildtype YF virus. This MAb was used in indirect immunofluorescence tests to identify wild-type antigenic variants in several different YF vaccine pools. Simultaneously, a vaccine-specific MAb prepared previously (MAb 864) was used to identify YF strain 17D vaccine type variants in the wild-type Asibi virus preparation. One variant, isolated by plaque purification from a 17D vaccine pool, possessed the wild-type epitope and was neurovirulent in infant mice whereas other variants, lacking the wild-type epitope but with vaccine-specific epitopes (identified by MAb 411), were avirulent in infant mice. Avirulent variants were able to infect mice and induce antibody. Virus-specific antigen was still detected in the brains of these mice 4 weeks after inoculation, suggesting that persistent infections were developing. These results to the potential risk of selection of wild-type variants in YF vaccine preparations. They also point to the potential risk of selection of wild-type variants in YF vaccine preparations and re-emphasize the need for modernization of techniques and more effective control measures to be taken during the production of YF vaccine.