Association of human cytomegalovirus (HCMV) neutralizing antibodies with antibodies to the HCMV glycoprotein complexes

Abstract

Background: Human cytomegalovirus (HCMV) causes asymptomatic infections, but also causes congenital infections when women were infected with HCMV during pregnancy, and life-threatening diseases in immunocompromised patients. To better understand the mechanism of the neutralization activity against HCMV, the association of HCMV NT antibody titers was assessed with the antibody titers against each glycoprotein complex (gc) of HCMV. Methods: Sera collected from 78 healthy adult volunteers were used. HCMV Merlin strain and HCMV clinical isolate strain 1612 were used in the NT assay with the plaque reduction assay, in which both the MRC-5 fibroblasts cells and the RPE-1 epithelial cells were used. Glycoprotein complex of gB, gH/gL complexes (gH/gL/gO and gH/gL/ UL128-131A [PC]) and gM/gN were selected as target glycoproteins. 293FT cells expressed with gB, gM/gN, gH/gL/ gO, or PC, were prepared and used for the measurement of the antibody titers against each gc in an indirect immunofluorescence assay (IIFA). The correlation between the IIFA titers to each gc and the HCMV-NT titers was evaluated. Results: There were no significant correlations between gB-specific IIFA titers and the HCMV-NT titers in epithelial cells or between gM/gN complex-specific IIFA titers and the HCMV-NT titers. On the other hand, there was a statistically significant positive correlation between the IIFA titers to gH/gL complexes and HCMV-NT titers. Conclusions: The data suggest that the gH/gL complexes might be the major target to induce NT activity against HCMV.

Antibody Titers Against Human Cytomegalovirus gM/gN and gB Among Pregnant Women and Their Infants

“…Transplacental transmission of anti-gM/gN antibodies to late preterm and full term infants was significantly lower than that of anti-gB antibodies. Human anti-gM/gN antibodies have been shown to neutralize CMV infection in-vitro and in a murine model but, similar to our findings, a recent study of non-pregnant CMV seropositive adults showed that anti-gM/gN titers did not correlate with in-vitro serum neutralizing activity ( 25 , 26 , 28 ). The reasons for the discrepancy between in-vitro and animal model data compared to clinical serologic responses are unclear, and it is unknown whether increasing human anti-gM/gN titers could improve serum CMV-neutralizing potential.…”

“…Glycoprotein M is the most abundant component of the viral proteome and is complexed to glycoprotein N, which exhibits sequence variation and glycosylation consistent with immune evasion functions (19)(20)(21)(22). This complex elicits antibodies with in vitro neutralizing capacity that are detectable among seropositive adults and in CMV hyperimmune globulin (19,(23)(24)(25)(26)(27). In mice, co-immunization with DNA vaccines encoding murine CMV (MCMV) gM and gN provided mice with complete protection against lethal MCMV challenge (28).…”

Affinity Tag Coating Enables Reliable Detection of Antigen-Specific B Cells in Immunospot Assays

“…Such LLPC and their secreted antibodies represent the first line of humoral defense against re-infection with pathogens such as seasonal influenza [12], Ebola [13], Dengue [14] and most recently the SARS-CoV-2 virus [15]. Moreover, pre-existing antibodies also serve to counter reactivation and subsequent dissemination of latent viral infections such as Epstein-Barr virus (EBV) [16] and human cytomegalovirus (HCMV) [17,18]. In this context, elevated levels of serum antibody reactivity serve as a reliable indicator of antigenic exposure.…”

Early immune surveillance to predict cytomegalovirus outcomes after allogeneic hematopoietic stem cell transplantation

“…Hence, HCMV IgM was not analyzed in this study. HCMV strain- or glycoprotein complex-specific neutralizing antibodies modulate HCMV infection by preventing binding of HCMV to target cells ( Martins et al., 2019 ; Shibamura et al., 2020 ). However, the method is complicated and has yet to be standardized.…”