The ability of eight neutralizing monoclonal antibodies (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 and the protection afforded by the MAbs and, secondly, the contribution of the host towards neutralization by the MAbs . The reduction in MCMV titre in the livers of BALB/c and C57BL/10 mice by the MAbs closely correlated with their neutralization titres . 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 prophylactically protected between 66 and 100% of mice from an intraperitoneal challenge with 4 LD MCMV regardless of their neutralization titre . The persistence of MCMV replication in the salivary gland was not prevented by either polyclonal Ig or MAbs. Despite the absolute requirement for complement for the neutralization of MCMV , both polyclonal Ig 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 addition, the extent to which the MAbs protected against MCMV could not be predicted from their immunoreactive or neutralizing titres or by their effect on splenic MCMV replication . Furthermore, these studies suggest that the mechanism(s) of neutralization of MCMV are different to those which act .


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