Comparison of Palivizumab-Like Antibody Binding to Different Conformations of the RSV F Protein in RSV-Infected Adult Hematopoietic Cell Transplant Recipients

Ye, Xunyan; Iwuchukwu, Obinna P.; Avadhanula, Vasanthi; Aideyan, Letisha; McBride, Trevor; Ferlic-Stark, Laura; Patel, Kalpesh; Piedra, Felipe Andrés; Shah, Dimpy P.; Chemaly, Roy F.; Piedra, Pedro A.

doi:10.1093/infdis/jiy026

Cited by 17 publications

(30 citation statements)

References 41 publications

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“…We have previously described the RSV-F antigenic site-specific serum antibody responses in RSV infected HCT recipients [23,24]. In this report, we extend our findings to include the serum and mucosal antibody response to p27 from RSV/A.…”

Section: Study Subjectssupporting

confidence: 69%

“…In this report, we extend our findings to include the serum and mucosal antibody response to p27 from RSV/A. In brief, the 33 HCT recipients with laboratory-confirmed RSV upper respiratory tract infections at enrollment and negative chest radiographic findings were enrolled within 72 hours of RSV diagnosis between January 2012 and April 2015 [23,24]. The RSV infected HCT recipients were stratified by level of risk for progression to the lower respiratory tract as previously described [23,24].…”

Section: Study Subjectsmentioning

confidence: 83%

“…In brief, the 33 HCT recipients with laboratory-confirmed RSV upper respiratory tract infections at enrollment and negative chest radiographic findings were enrolled within 72 hours of RSV diagnosis between January 2012 and April 2015 [23,24]. The RSV infected HCT recipients were stratified by level of risk for progression to the lower respiratory tract as previously described [23,24]. To evaluate serum and mucosal antibodies against p27, serum and nasal wash samples were collected at enrollment (acute samples) and 14-60 days after enrollment (convalescent samples).…”

Section: Study Subjectsmentioning

confidence: 99%

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Antibody Response to the Furin Cleavable Twenty-Seven Amino Acid Peptide (p27) of the Fusion Protein in Respiratory Syncytial Virus (RSV) Infected Adult Hematopoietic Cell Transplant (HCT) Recipients

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Iwuchukwu

et al. 2020

Vaccines

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Background: Cleavage of the inactive precursor fusion protein (F0) of respiratory syncytial virus (RSV) at two furin-recognition sites is required for membrane fusion activity, and the cleavage releases the twenty-seven amino acid peptide (p27). However, a recent study shows that p27 was an immunodominant epitope in RSV infected children, indicating that p27 was recognized as an immunogen. In the present study, we investigated the immunogenicity of p27 in an immunocompromised population of adults by measuring serum and mucosal antibody responses to p27 in samples from adult hematopoietic cell transplant (HCT) recipients. Methods: We prospectively enrolled a cohort of RSV infected HCT recipients. Serum and nasal-wash samples were obtained within the first week of RSV infection (acute) and 3 to 5 weeks post-infection (convalescent). We quantified the serum and mucosal IgG and IgA anti-p27 antibodies by a RSV/A p27 peptide enzyme-linked immunosorbent assay (ELISA) and serum and mucosal p27 like antibodies (P27LA) by a p27 competitive antibody (P27CA) assay. Results: The lower limit of detection for the ELISA and P27CA assays was 0.2 and 50 ng/mL, respectively with no cross-reaction detected with a panel of monoclonal antibodies targeting pre-fusion and post-fusion antigenic sites. P27 antibodies were detected at nanogram concentration in sera and nasal washes in the majority of RSV infected HCT recipients. However, there was no significant difference in the geometric mean antibody concentrations between the acute and convalescent sera (except for serum P27LA), between HCT recipients who shed RSV <14 days and ≥14 days, as well as between RSV/A and RSV/B infected HCT recipients. In addition, approximately 30% of HCT recipients had a 4-fold or greater decrease in mucosal IgG and IgA anti-p27 antibodies during viral clearance. Conclusion: In conclusion, in RSV naturally infected adult HCT recipients, the antibodies against p27 were detectable in both serum and nasal wash samples with higher concentration in serum than that in nasal washes. However, nearly 30% of RSV infected HCT recipients had a significant decrease in their mucosal anti-p27 antibody, suggesting that IgG and IgA anti-p27 antibodies were binding to either free viruses or RSV infected cells containing p27, and that anti-p27 antibodies in the respiratory tract were part of the mucosal antibody response in controlling RSV infection.

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Section: Study Subjectssupporting

confidence: 69%

Section: Study Subjectsmentioning

confidence: 83%

Section: Study Subjectsmentioning

confidence: 99%

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Antibody Response to the Furin Cleavable Twenty-Seven Amino Acid Peptide (p27) of the Fusion Protein in Respiratory Syncytial Virus (RSV) Infected Adult Hematopoietic Cell Transplant (HCT) Recipients

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Iwuchukwu

et al. 2020

Vaccines

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“…Both were enrolled well into their illness, at 9 and 25 days, giving them time to develop an RSV specific immunological response. This is also evident by their comparatively greater levels of neutralizing antibodies and palivizumab-like antibodies [9,33]. Three women who were re-enrolled and had paired sera, exhibited an RSV infection profile despite negative PCR.…”

Section: Discussionmentioning

confidence: 90%

“…Palivizumab Competitive Antibody Assay (PCA): A PCA assay was performed as previously described to detect the concentration of palivizumab-like antibodies (PLA) that compete with biotinylated palivizumab for binding to antigenic site II of the fusion protein of RSV [24]. The source of the fusion protein was from sucrose purified RSV/A/Bernett (GA1 genotype) that was coated onto the 96-well plate for 18 h. The lower limit of detection was 1 lg/mL.…”

Section: Case Definitions Pcr and Serological Assaysmentioning

confidence: 99%

Clinical characteristics and outcomes of respiratory syncytial virus infection in pregnant women

Hause

Avadhanula

Maccato

et al. 2019

Vaccine

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a b s t r a c tObjective: To describe the clinical presentation and laboratory diagnosis of pregnant women with respiratory syncytial virus (RSV) infection. Methods: Pregnant women in their second and third trimester were enrolled during the course of routine prenatal care visits when they were asymptomatic within the preceding two weeks (healthy controls) or when they reported symptoms of acute respiratory illness (ARI) of 7 days of duration (cases). Clinical outcomes were assessed at enrollment and two weeks after. Re-enrollment was allowed. Nasalpharyngeal secretions were evaluated for respiratory pathogens by real-time reverse transcription polymerase chain reaction (PCR). Sera were tested for RSV-specific antibody responses by Western Blot, microneutralization assay, and palivizumab competitive antibody assay. Results: During the 2015-2016 respiratory virus season, 7 of 65 (11%) pregnant women with ARI at their initial enrollment and 8 of 77 (10%) pregnant women with ARI during the study period (initial or reenrollment) had PCR-confirmed RSV infection. Four (50%) PCR-confirmed RSV ARI cases reported symptoms of a lower respiratory tract illness (LRTI), one was hospitalized. Combining PCR and serology data, the RSV attack rate at initial enrollment was 12% (8 of 65), and 13% (10 of 77) based on ARI episodes. Among healthy controls, 28 of 88 (32%) had a Western Blot profile suggestive of a recent RSV infection either in the prior and/or current season. Conclusion: RSV had an attack rate of 10-13% among ambulatory pregnant women receiving routine prenatal care during the respiratory virus season. The serology results of healthy controls suggest a potentially higher attack rate. Future studies should be aware of the combined diagnostic strength of PCR and serology to identify RSV infection. As maternal RSV vaccine candidates are evaluated to protect young infants, additional priority should be placed on outcomes of pregnant women.

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Respiratory Viral Infections

Boghdadly

Ogimi

Boeckh

2023

Pulmonary and Critical Care Considerations of Hematopoietic Stem Cell Transplantation

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Comparison of Palivizumab-Like Antibody Binding to Different Conformations of the RSV F Protein in RSV-Infected Adult Hematopoietic Cell Transplant Recipients

Abstract: F protein conformation does not appear to have a measurable impact on PCA assays for measuring PLA induced by RSV/A or RSV/B infection.

Cited by 17 publications

References 41 publications

Antibody Response to the Furin Cleavable Twenty-Seven Amino Acid Peptide (p27) of the Fusion Protein in Respiratory Syncytial Virus (RSV) Infected Adult Hematopoietic Cell Transplant (HCT) Recipients

Antibody Response to the Furin Cleavable Twenty-Seven Amino Acid Peptide (p27) of the Fusion Protein in Respiratory Syncytial Virus (RSV) Infected Adult Hematopoietic Cell Transplant (HCT) Recipients

Clinical characteristics and outcomes of respiratory syncytial virus infection in pregnant women

Respiratory Viral Infections

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