Effect of virulence on immunogenicity of single and double vaccinia virus recombinants expressing differently immunogenic antigens: antibody-responseinhibition induced by immunization with a mixture of recombinants differing in virulence

It has been shown recently that the residual virulence of vaccinia virus (V V) is an important factor that influences the outcome of immunization with VV recombinants. This study focused on the correlation of the residual viru lence of several VV recombinants with antibody responses against the strong ly immunogenic extrinsic glycoprotein E of varicella-zoster virus and the w eakly immunogenic extrinsic protein preS2-S of hepatitis B virus and agains t VV proteins, with mice used as a model organism. Furthermore, the effects of mixing different recombinants on the antibody response were studied. Th e results obtained indicated that: (i) the antibody response depended on th e residual virulence of the recombinants, more so in the case of the weakly immunogenic protein; (ii) the residual virulence, the growth rate of the V V recombinants in extraneural tissues and the immunogenicity were associate d features; (iii) immunization with mixtures of two differently virulent re combinants or with unequal amounts of two similarly virulent recombinants s ometimes led to the suppression of antibody response. The appearance of thi s suppression was dependent on three factors: the residual virulence of the recombinants, the immunogenicity of the extrinsic proteins and the ratio o f the recombinants in the mixtures. Thus, the data obtained demonstrate tha t there are various limitations to the use of replicating VV recombinants f or immunization purposes.