Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Apr 7;221(9):1470-1479.
doi: 10.1093/infdis/jiz596.

Cytomegalovirus Humoral Response Against Epithelial Cell Entry-Mediated Infection in the Primary Infection Setting After Hematopoietic Cell Transplantation

Danniel Zamora  1   2 , Elizabeth M Krantz  1 , Margaret L Green  1   2 , Laurel Joncas-Schronce  1 , Rachel Blazevic  1 , Bradley C Edmison  1 , Meei-Li Huang  3 , Terry Stevens-Ayers  1 , Keith R Jerome  1   3 , Adam P Geballe  4   5 , Michael Boeckh  1   2
Affiliations
Randomized Controlled Trial

Cytomegalovirus Humoral Response Against Epithelial Cell Entry-Mediated Infection in the Primary Infection Setting After Hematopoietic Cell Transplantation

Danniel Zamora et al. J Infect Dis. .

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.

Keywords: CMV; cytomegalovirus; hematopoietic cell transplantation; neutralizing antibodies; pentameric complex.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Distribution of weekly CMV nAb titers. Distribution of CMV neutralizing antibody dilution titer by post-transplant week and study arm. The dashed horizontal line represents the assay limit of quantification (LoQ), a neutralizing antibody dilution titer of 32 (or 5 on log2 scale). Dilution titers <32 were set to half LoQ on the log2 scale and negative values were set to 1; values have been jittered to allow viewing of overlapping data points. Shaded boxes represent the interquartile range and black horizontal bars within boxes represent the median. Numbers below the boxplots show the number of patients contributing data to each summary. In cases where patients contributed more than one sample in a given week, mean values are shown. Data beyond week 10 were excluded from this figure due to small sample size.
Figure 2.
Figure 2.
Proportion of patients with CMV infection. Percentage of patients with CMV (A) IU/mL ≥ 50 IU/mL, (B) ≥ 1000 IU/mL, and (C) ≥ 10 000 IU/mL in each study week, by study arm. (D) Maximum CMV IU/mL detected for each study week, by study arm.
Figure 3.
Figure 3.
Cumulative incidence of CMV infection. Cumulative incidence of CMV infection quantitative CMV PCR at viral load thresholds of (A) ≥ 50 IU/mL, (B) ≥ 1,000 IU/mL, and (C) ≥ 10 000 IU/mL. A total of 25 of 53 patients met CMV infection criteria at the lowest viral load cutoff of ≥ 50 IU/mL (12 CMV IVIG, 13 control), 19 of 53 patients met CMV infection criteria at the viral load cutoff of ≥ 1000 IU/mL (7 CMV IVIG arm, 12 control), and 16 of 53 patients met CMV infection criteria at the highest viral load cutoff of ≥ 10 000 IU/mL (5 CMV IVIG arm, 11 control). Numbers shown below the x-axis represent the number of patients at risk for CMV infection.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest 2011; 121:1673–80. - PMC - PubMed
    1. Wang D, Shenk T. Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J Virol 2005; 79:10330–8. - PMC - PubMed
    1. Wang D, Shenk T. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 2005; 102:18153–8. - PMC - PubMed
    1. Hahn G, Revello MG, Patrone M, et al. . Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 2004; 78:10023–33. - PMC - PubMed
    1. Ryckman BJ, Rainish BL, Chase MC, et al. . Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells. J Virol 2008; 82:60–70. - PMC - PubMed

Publication types

MeSH terms