Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

doi:10.1126/science.aat0066

. 2019 Jan 18;363(6424):288-293.

doi: 10.1126/science.aat0066.

Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Jose Paulo Martins^#^{1

2}, Christopher E Andoniou^#^{3

4

5}, Peter Fleming^#^{3

4}, Rachel D Kuns¹, Iona S Schuster^{3

4

5}, Valentina Voigt^{3

4}, Sheridan Daly^{3

4}, Antiopi Varelias¹, Siok-Keen Tey¹, Mariapia A Degli-Esposti^#^{6

4

5}, Geoffrey R Hill^#^{7

8

9}

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
² School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
³ Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia.
⁴ Centre for Experimental Immunology, Lions Eye Institute, Perth, Western Australia, Australia.
⁵ Infection and Immunity Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
⁶ Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia. mariapia@lei.org.au grhill@fredhutch.org.
⁷ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. mariapia@lei.org.au grhill@fredhutch.org.
⁸ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁹ Division of Medical Oncology, University of Washington, Seattle, WA, USA.

^# Contributed equally.

PMID: 30655443
DOI: 10.1126/science.aat0066

Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

Jose Paulo Martins et al. Science. 2019.

. 2019 Jan 18;363(6424):288-293.

doi: 10.1126/science.aat0066.

Authors

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
² School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
³ Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia.
⁴ Centre for Experimental Immunology, Lions Eye Institute, Perth, Western Australia, Australia.
⁵ Infection and Immunity Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
⁶ Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia. mariapia@lei.org.au grhill@fredhutch.org.
⁷ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. mariapia@lei.org.au grhill@fredhutch.org.
⁸ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁹ Division of Medical Oncology, University of Washington, Seattle, WA, USA.

^# Contributed equally.

PMID: 30655443
DOI: 10.1126/science.aat0066

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.

Keywords: BMT; GVHD; CMV.

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Comment in

B cells, CMV, and stem cell transplant.
Alegre ML. Alegre ML. Science. 2019 Jan 18;363(6424):232-233. doi: 10.1126/science.aav9867. Science. 2019. PMID: 30655432 No abstract available.

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Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

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Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation

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