Differential kinetics of human cytomegalovirus load and antibody responses in primary infection of the immunocompetent and immunocompromised host

Abstract

The comparative long-term kinetics of human cytomegalovirus (HCMV) load and HCMV-specific antibody responses in the immunocompetent and immunocompromised solid-organ transplanted host during primary HCMV infection was investigated. In total, 40 immunocompetent subjects and 17 transplanted patients were examined for viral load as well as for IgG antibody responses to HCMV glycoproteins gH/gL/pUL128L, gH/gL and gB, and neutralizing antibodies in ARPE-19 epithelial cells and human fibroblasts. In parallel, the CD4 + and CD8 + HCMV-specific T-cell responses were determined by cytokine flow cytometry. Transplanted patients reached significantly higher viral DNA peaks, which persisted longer than in immunocompetent subjects. The ELISA-IgG responses to the pentamer, gH/gL and gB were significantly higher in primary infections of the immunocompetent until six months after onset, with the two antibody levels then overlapping from six to 12 months. Antibody levels neutralizing infection of epithelial cells were significantly higher in transplanted patients after six months, persisting for up to a year after transplantation. This trend was not observed for antibodies neutralizing infection of human fibroblasts, which showed higher titres in the immunocompetent over the entire one-year followup. In conclusion, in immunocompromised patients the viral load peak was much higher, while the neutralizing antibody response exceeded that detected in the immunocompetent host starting six months after onset of follow-up, often concomitantly with a lack of specific CD4 + T cells. In this setting, the elevated antibody response occurred in the presence of differentiated follicular helper T cells in the blood, which decreased in number as did antibody titres upon reappearance of HCMV-specific CD4 + T cells.

Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients

“…Preliminary observations showed that both neutralizing and ELISA IgG antibody titres to the HCMV glycoprotein pentamer gHgLpUL128L and its components and to glycoprotein B (gB) were higher in the Tx patient (Gerna et al, 2015). However, it has recently been shown by our group that antibodies to the pentamer are mostly highly neutralizing, whereas antibodies to gB are mostly non-neutralizing (Kabanova et al, 2014).…”

“…In the period 2012-2014, 40 Ic (36 pregnant women and 4 non-pregnant patients) and 20 solid-organ Tx patients (10 kidney, 8 heart, 1 lung, and 1 heart-lung transplant recipient) with primary HCMV infection were enrolled in the study for 1-2 year follow-up. Among them, 26 Ic and 16 Tx patients were preliminarily analysed in our previous study on the kinetics of the antibody response in primary HCMV infection (Gerna et al, 2015). In addition, 22 HCMV-seropositive Tx patients (8 heart and 14 kidney transplant recipients) with reactivated HCMV infection were included in the study.…”

Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity

“…However, the serum levels of these virus-specific IgG antibodies eventually decline. Longitudinal follow-up of HCMVinfected individuals indicates that HCMV-specific antibodies with different specificities expand over time (28,29), suggesting similar mechanisms underlying antibody inflation. Gradual antibody accumulation likely is related to viral persistence, as it is not observed in various acute infections with influenza virus (30), vesicular stomatitis virus (31), and LCMV Armstrong (32).…”

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

“…[140]. The higher median peak antibody titre in primary infection of SOTR appeared to be related to the sustained presence of activated (ICOS + PD-1 ++ ) circulating follicular helper T (T FH ) cells in the absence of detectable HCMV-specific effector CD4 + T cells in blood and the presence of HCMV DNAemia [141].…”