Protection against murine cytomegalovirus infection by passive transfer of neutralizing and non-neutralizing monoclonal antibodies

The ability of eight neutralizing monoclonal ntibodies (MAbs) specific for structural proteins of murine cytomegalovirus (MCMV) to protect mice passively against MCMV infection was examined to determine firstly whether a correlation existed between the neutralization titres of the MAbs in vitro and the protection afforded by the MAbs in vivo and, secondly, the contribution of the host towards neutralization by the MAbs in vivo. The reduction in MCMV titre in the livers of BALB/c and C57BL/10 mice by the MAbs closely correlated with their neutralization titres in vitro. However, in the spleens of BALB/c mice, in which MCMV replicates to high titre, almost all of the MAbs tested were ineffective in reducing MCMV replication. Indeed, a significant increase in splenic MCMV replication was observed in mice treated 24 h prior to MCMV replication with either neutralizing MAbs or polyclonal Ig. Each of six MAbs prophylacti-cally protected between 66 and 100 % of mice from an intraperitoneal challenge with 4 LDs0 MCMV regard-less of their neutralization titre in vitro. The persistence of MCMV replication in the salivary gland was not prevented by either polyelonal Ig or MAbs. Despite the absolute requirement for complement for the neutral-ization of MCMV in vitro, both polyclonal lg and MAb 4F9 protected A/J mice, which are deficient in the fifth component of complement, as efficiently as they did complement competent BALB/c mice. These results demonstrate that MAbs specific for single MCMV polypeptides are protective in vivo. In addition, the extent o which the MAbs protected against MCMV could not be predicted from their immunoreactive or neutralizing titres in vitro or by their effect on splenic MCMV replication in vivo. Furthermore, these studies suggest hat the mechanism(s) of neutralization of MCMV in vitro are different to those which act in vivo