A phase I trial of epstein-barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation.
BACKGROUND.: Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative disease after transplantation. METHODS.: A phase I trial recruited children with chronic kidney disease to two successive cohorts given three injections of 12.5 microg (n=6) and 25 microg (n=10) recombinant gp350/alhydrogel vaccine over 6 to 8 weeks. RESULTS.: One in each cohort acquired wild EBV before the week 28 evaluation. Both doses were similarly immunogenic, inducing an IgG response in all 13 evaluable patients. Neutralizing antibodies were detected in four recipients (1/4 in the 12.5 microg and 3/9 in the 25 microg cohort). Median time from first vaccination to transplantation was 24 weeks. Immune responses declined rapidly and were unlikely to affect posttransplant events. DISCUSSION.: The vaccine was immunogenic but a prolonged vaccine schedule up to time of transplantation or improved adjuvants are required in future trials to reduce posttransplant EBV load and risk of lymphoproliferative disease.
Paediatric Nephrology, Great Ormond Street Hospital for Sick Children NHS Trust, London, United Kingdom.
Lesley
L
Rees
E Jane
EJ
Tizard
Andrew J
AJ
Morgan
W David
WD
Cubitt
Susan
S
Finerty
Titilade A
TA
Oyewole-Eletu
Karen
K
Owen
Collin
C
Royed
Servi J
SJ
Stevens
Rukshana C
RC
Shroff
Manjit K
MK
Tanday
A Douglas
AD
Wilson
Jaap M
JM
Middeldorp
Peter L
PL
Amlot
Neil M
NM
Steven
D000293:Adolescent; D000818:Animals; D016466:CHO Cells / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007223:Infant; D007676:Kidney Failure, Chronic / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000633:toxicity*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000633:toxicity*
C034059:GP 300-350, Epstein-Barr virus; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D014765:Viral Vaccines