Danniel Zamora1,2, Elizabeth M Krantz1, Margaret L Green1,2, Laurel Joncas-Schronce1, Rachel Blazevic1, Bradley C Edmison1, Meei-Li Huang3, Terry Stevens-Ayers1, Keith R Jerome1,3, Adam P Geballe4,5, Michael Boeckh1,2. 1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 2. Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington. 3. Department of Laboratory Medicine, University of Washington, Seattle, Washington. 4. Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington. 5. Departments of Medicine and Microbiology, University of Washington, Seattle, Washington.
Abstract
BACKGROUND: The influence of humoral immunity on the prevention of primary cytomegalovirus (CMV) infection after hematopoietic cell transplantation (HCT) is poorly understood. METHODS: To determine whether neutralizing antibodies (nAbs) against CMV pentameric complex (PC)-mediated epithelial cell entry decrease CMV infection after HCT, samples were analyzed from a randomized controlled trial of CMV intravenous immunoglobulin (IVIG) prophylaxis. Weekly serum from 61 CMV donor-positive/recipient-negative (D+/R-) HCT patients (33 control, 28 CMV IVIG) was tested using a PC-entry nAb assay and quantitative CMV polymerase chain reaction (PCR). RESULTS: There was a trend toward higher weekly PC-entry nAb titers (P = .07) and decreased CMV infection by PCR at viral load cutoffs of ≥1000 and ≥10 000 IU/mL in the CMV IVIG arm. High nAb titers were not significantly protective against CMV infection later after HCT in both study arms. Among CMV-infected patients, each log2 increase in nAb titer was associated with an average 0.2 log10 decrease in concurrent CMV viral load after infection (P = .001; adjusted for study arm). CONCLUSIONS: This study provides initial support that CMV IVIG prophylaxis moderately enhances PC-entry nAB activity in D+/R- HCT recipients.
RCT Entities:
BACKGROUND: The influence of humoral immunity on the prevention of primary cytomegalovirus (CMV) infection after hematopoietic cell transplantation (HCT) is poorly understood. METHODS: To determine whether neutralizing antibodies (nAbs) against CMV pentameric complex (PC)-mediated epithelial cell entry decrease CMV infection after HCT, samples were analyzed from a randomized controlled trial of CMV intravenous immunoglobulin (IVIG) prophylaxis. Weekly serum from 61 CMV donor-positive/recipient-negative (D+/R-) HCT patients (33 control, 28 CMV IVIG) was tested using a PC-entry nAb assay and quantitative CMV polymerase chain reaction (PCR). RESULTS: There was a trend toward higher weekly PC-entry nAb titers (P = .07) and decreased CMV infection by PCR at viral load cutoffs of ≥1000 and ≥10 000 IU/mL in the CMV IVIG arm. High nAb titers were not significantly protective against CMV infection later after HCT in both study arms. Among CMV-infected patients, each log2 increase in nAb titer was associated with an average 0.2 log10 decrease in concurrent CMV viral load after infection (P = .001; adjusted for study arm). CONCLUSIONS: This study provides initial support that CMV IVIG prophylaxis moderately enhances PC-entry nAB activity in D+/R- HCT recipients.
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