Circulating antibody-secreting cells during acute respiratory syncytial virus infection in adults

Abstract

Background: The specificity and duration of circulating human antibody-secreting cells (ASCs) after vaccination have been well described, but characteristics of ASCs during acute respiratory infections have not been well studied.

Methods: Circulating antigen-specific ASCs were measured at 3 time points (enrollment, days 10-16, and days 22-45) in 40 adults during respiratory syncytial virus (RSV) infection.

Results: Of the 40 patients, 36 (90%) had detectable circulating RSV F protein-specific ASCs within 11 days after illness onset. The magnitude of the RSV-specific ASCs was 1-1500 spots per 10⁶ peripheral blood mononuclear cells (mean frequency [± standard deviation], 200 ± 256 spots per 10⁶ peripheral blood mononuclear cells). ASCs were detected on day 8-16 and day 22-45 after symptom onset in 78% and 48% of subjects, respectively. Subjects shedding virus for >10 days were more likely to have a positive response to ASC enzyme-linked immunospot assay at the late time point than those shedding for ≤10 days (8 of 12 subjects vs 2 of 11 subjects; P = .02).

Conclusions: The kinetics of ASC circulation during acute mucosal viral infections was more prolonged than that we had observed after a single intramuscular injection with inactivated influenza vaccine in a study reported elsewhere. The association between the duration of virus shedding and the persistence of detectable viral-specific ASCs suggests that ongoing antigen persistence induces a prolonged temporal pattern of ASC generation.

Table 1.

Demographic, Clinical, and Virological Characteristics of 40 Subjects Infected with Respiratory Syncytial Virus (RSV)

Figure 1.

Respiratory syncytial virus shedding patterns for the 40 subjects, with peak viral titer in nasal secretion samples on the y-axis and days of viral shedding on the x-axis. PFU, plaque-forming unit.

Figure 2.

Response to enzyme-linked immunospot assay for circulating antibody-secreting cells during acute respiratory syncytial virus (RSV) infection in 2 patients (panels A and B)onday 4or5, 11or 12, and25 after symptom onset. Assays were specific for the following antigens: RSV F protein, influenza virus, bovine serum albumin (BSA; 300,000 peripheral blood mononuclear cells [PBMCs] per well for each), and total immunoglobulin G (IgG; 100,000 PBMCs per well). Nasal swab samples were positive for RSV by polymerase chain reaction for 16 and 20 days after symptom onset for the patient whose results are shown in panel A and the patient whose results are shown in panel B, respectively.

Figure 3.

Numbers of antibody-secreting cells (ASCs) specific to respiratory syncytial virus (RSV) in blood samples of 40 patients with acute infection confirmed by reverse-transcription polymerase chain reaction, according to number of days after symptom onset. Each filled symbol represents a single patient. Open triangles represent 2 time points for a single patient who had a negative RSV-specific ASC response on day 7 and a positive response on day 10. The horizontal dotted line represents the threshold for a positive RSV-specific ASC response (>13 spots per 10⁶ peripheral blood mononuclear cells [PBMCs]).

Figure 4.

Respiratory syncytial virus (RSV)-specific antibody-secreting cell (ASC) frequencies in blood samples from the 40 patients with acute RSV infection, by days after symptom onset. A, Patients shedding virus for ⩽10 days. B, Patients shedding virus for >10 days. The dotted line represents the threshold for a positive RSV-specific ASC response (>13 spots per 10⁶ peripheral blood mononuclear cells [PBMCs]).

Figure 5.

Enzyme-linked immunospot assay frequencies of respiratory syncytial virus (RSV)-specific antibody-secreting cells in blood samples obtained at late time points in RSV-infected patients who did (plus sign) or did not (minus sign) receive corticosteroids for acute treatment. PBMC, peripheral blood mononuclear cells.

Figure 6.

Graphic display of temporal pattern of positive (filled bars) and negative (open bars) respiratory syncytial virus (RSV)-specific antibody-secreting cell (ASC) assays in all blood samples from all RSV-infected subjects.