Characteristics of Antibody Responses in West Nile Virus-Seropositive Blood Donors

Abstract

The production of WNV-specific IgM and IgG antibodies is important for both the diagnosis and the clearance of WNV infection (4). The persistence of IgG antibodies is thought to confer protection from subsequent reinfection (4-6). In a study of 245 viremic blood donors, IgM antibodies persisted for a mean of 156 days, and IgG antibodies persisted at the same titer for at least 1 year postinfection (7). IgM antibodies persisted in up to 17% of subjects at 400 days postinfection, whereas IgG antibodies were maintained at high levels based on enzyme immunoassay (EIA) signal-to-cutoff levels among all subjects. It is unclear if antibodies persist beyond that time, if those antibodies are specific for and neutralize WNV, and if antibody responses and persistence vary depending on age or sex.We studied the characteristics of WNV antibody responses in two different groups of blood donors, one identified by a crosssectional serosurvey and the second by a longitudinal follow-up of donors detected during acute viremia by blood donor screening for WNV RNA. We compared the antibody levels in donors with recent versus more remote infections and looked at differences according to age and sex. We also assessed the specificity and neutralizing capacities of the antibody responses. MATERIALS AND METHODSThis study was approved by the institutional review boards of the participating institutions, and all subjects agreed to participate and signed informed consents. Blood donors who were seropositive for WNV IgG antibodies were identified from a previously reported serosurvey of Ͼ4,500 North Dakota blood donors (2). In that study, 370 donors (8.2%) were IgG positive, and 28 of those (7.5%) were also IgM positive. The durability of the antibody responses was assessed by comparing IgG antibody levels among recently infected donors (those who were IgM seropositive) versus donors presumed to be infected Ͼ1 year prior (i.e., were IgM negative). The specificity and neutralizing capacity of the antibody response were assessed by assaying a subset (54 samples across the range of IgG response) of samples from seropositive donors using a WNV plaque reduction neutralization assay to quantify plaque reduction neutralization titers. These samples were selected by choosing every 6th sample from the lowest to highest titers across the IgG response spectrum from 324 samples with adequate volume remaining for plaque reduction neutralization testing (PRNT).We also studied a group of 18 donors who were originally identified with acute WNV infection by screening for blood plasma RNA with nucleic acid amplification technology (NAT) in 2005 and who were enrolled in a 1-year longitudinal follow-up study (7). Their WNV IgG, IgM, and PRNT levels were assessed at 6 months and 5 years postinfection. These samples were tested in parallel and under code to minimize interrun variability and biases in assay performance and interpretation.Blood plasma specimens were tested for WNV IgM and IgG by using Food and Drug Administration-approved enzyme-linked immunosorb...

Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing

“…These results have limited power due to the relatively small sample size of four post-convalescent subjects and seven recently infected subjects. However, they are supported by previous studies where WNV-specific serum antibodies were detected in subjects up to 8 years post-infection 26,31,32,36,38 . Persistence of serum antibodies specific to other viral infections and vaccines (e.g.…”

West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety

“…22–26 Even though, a group at the FDA reported that infectious WNV could be amplified by co-cultivating whole blood collected months after index donation with Vero cells and monocyte-derived cells despite the presence of anti-WNV antibodies, 16,27,28 only one out of thousands units collected in the seropositive convalescent stage of WNV infection. 9,29 has ever been linked to a breakthrough infection Therefore it is probably reasonable to assume that WNV particles persisting at low levels bound to RBC in whole blood are neutralized after the development of anti-WNV antibodies. However, the recent exception is a case of WNV transfusion-transmission that occurred in 2012 and had a fatal outcome despite donor seroconversion to anti-WNV IgM antibodies; 30 This patient, who had non-Hodgkin's lymphoma, chemotherapy and an autologous stem cell transplant, received allogenic, leukoreduced, irradiated blood products collected from multiple donors including a donor who had tested non-reactive for WNV RNA by TMA and had seroconverted to anti-WNV IgM antibodies.…”

West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications

“…Papa et al [ 361 ] reported the persistence of WNV IgM and IgG for up to three years post-infection in humans. Another study conducted in WVN seropositive blood donor volunteers reported neutralising antibodies in 94.4% (n = 54) for as long as five years post infection [ 362 ]. However, the results of this study should not be generalised given that the study sample involved individuals who voluntarily participated, thus, might not be truly representative of the population at large.…”