Immunoglobulins have been repeatedly applied to treat human cytomegalovirus (HCMV) infections, but without clear evidence of clinical efficacy. One explanation for these disappointing results is the limited neutralizing potency of the immunoglobulins used. An increase in the neutralizing antibody titers of the treated patients has also not yet been demonstrated.

In a Phase I clinical trial, we tested whether the transfer of plasma from previously identified blood donors who neutralize HCMV exceptionally well (HCMV elite neutralizers) can increase the neutralization capacity in the serum of treated patients.

The study included 12 stem cell transplant recipients who were HCMV seronegative and thus at risk for HCMV reactivation and disease. Patients received one or two plasma units of elite neutralizers in each of four treatment weeks. Serum samples were collected from patients before and after treatment and on days 2 and 4 of the treatment week. As a primary endpoint, neutralization titers in patients' serum samples were determined with an immunofluorescence-based assay using HCMV strain TB40/E, resulting in time curves of neutralization titers over the entire treatment period. Correlation analyses were performed to investigate whether the increase achieved by the treatment correlates with the neutralization capacity of the transferred plasma units. To analyze strain-specific differences, samples from before and after treatment were re-evaluated with seven laboratory strains representing almost all glycoprotein genotypes.

On average, the transfused plasma units had an approximately 10-fold higher mean neutralizing capacity than the patients' sera. The combined curves of all patients showed that the plasma transfusion increased the neutralization capacity of the patients, on average by 83% immediately after transfusion and by 33% after one week. Over a period of four weeks, the cumulative increase in neutralization titer was 132%. The increase achieved in individual patients was highly variable and correlated with low baseline titers of the patients and high titers of the transferred plasma.

Adoptive transfer of anti-HCMV antibodies can increase neutralization titers in a relevant patient group. Patients with a low neutralization capacity may benefit from the transfer of neutralizing antibodies, whereas patients with a high neutralization capacity will probably not.

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