2591. The Role of Neutralizing Antibodies (nAb) Against Cytomegalovirus (CMV) Epithelial Cell-entry in Patients with Self-limited (SL) CMV infection after Hematopoietic Cell Transplantation (HCT)

Abstract

BackgroundCMV transmission after HCT occurs in 20–30% of CMV-seronegative recipients with CMV-seropositive donors (i.e., CMV D+/R−) and a distinct subset develop transient CMV DNAemia without progression to culture positivity in the absence of antivirals (BMT 1992; 9:221; J Med Virol 2019; 91:1128). The mechanism of SL CMV infection is unknown but may involve nAb, which have been implicated in primary viral clearance, including nAb that inhibit viral epithelial and endothelial cell-entry via CMV pentameric complex (PC). We aimed to describe viral kinetics and the influence of nAb on CMV infection progression in SL CMV-infected patients and controls within a unique cohort from the pre-antiviral era.MethodsWeekly serum samples from 456 CMV D+/R− allogeneic HCT patients collected between 1978–95 were screened using quantitative CMV DNA PCR. Patients with CMV DNAemia in the first 100 days after HCT followed by a sustained return to undetectable levels without positive surveillance CMV cultures were defined as having SL CMV infection. SL CMV-infected patients were matched 1:1:1 to CMV-infected controls (patients with CMV infection by culture in the same period after HCT ± 14 days) and non-infected controls (patients without CMV DNA or culture positivity) to compare viral kinetics and nAb. A modified nAb assay was used to evaluate serum nAb activity against CMV PC-mediated cell entry (Vaccine 2008; 26:5760; JID 2019; in press).ResultsWe identified 9 patients with SL CMV infection and baseline demographics are shown (Table 1). SL CMV-infected patients had a median of 21 days (range 7–54 days) until first positive CMV DNAemia. The median peak CMV DNAemia was 94.2 IU/mL (range 40.2–225.9 IU/mL) and 46,118 IU/mL (range 1,132–284,362 IU/mL) in SL CMV-infected and CMV-infected controls respectively. There was no difference in nAb titers between groups at infection day 0 or in the preceding 4 weeks (Figure 1, Figure 2).ConclusionnAb against CMV PC-mediated cell entry did not appear to play a critical role in viral clearance in SL CMV infection after CMV D+/R- allogeneic HCT. Our study illustrates the potential for clearance of relatively low CMV DNAemia after HCT without the addition of antivirals. CMV-specific T-cell immunity or innate immune mechanisms may be more important in early viral control. Disclosures All authors: No reported disclosures.