Polyomavirus BK neutralizing activity in human immunoglobulin preparations.
BACKGROUND
Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness.


METHODS
We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture.


RESULTS
Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus.


CONCLUSIONS
Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection.
Randhawa
Parmjeet S
PS
Division of Transplantation Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. randhawapa@msx.upmc.edu
Schonder
Kristine
K
Shapiro
Ron
R
Farasati
Nousha
N
Huang
Yuchen
Y
D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry; D001739:BK Virus / Q000378:metabolism*; D002417:Cattle; D006224:Cricetinae; D004279:DNA, Viral / Q000378:metabolism; D006509:Hepatitis B / Q000628:therapy; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D051379:Mice; D027601:Polyomavirus Infections / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D012709:Serum Albumin / Q000737:chemistry; D013997:Time Factors
D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D012709:Serum Albumin