Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Jose Paulo Martins, Christopher E. Andoniou, Peter Fleming, Rachel D. Kuns, Iona S. Schuster, Valentina Voigt, Sheridan Daly, Antiopi Varelias, Siok-Keen Tey, Mariapia A. Degli-Esposti, Geoffrey R. Hill

Research output: Contribution to journalArticlepeer-review

31 Citations (Web of Science)

Abstract

Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the mechanisms for cytomegalovirus reactivation after transplantation and identify a readily translatable strategy of exceptional potency, which avoids the constraints of cellular therapies.

Original languageEnglish
Pages (from-to)288-293
Number of pages6
JournalScience
Volume363
Issue number6424
DOIs
Publication statusPublished - 18 Jan 2019

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