Species-Specific and Cross-Reactive IgG1 Antibody Binding to Viral Capsid Protein 1 (VP1) Antigens of Human Rhinovirus Species A, B and C

Iwasaki, Jua; Smith, Wendy-Anne; Stone, Shane R.; Thomas, Wayne R.; Hales, Belinda J.

doi:10.1371/journal.pone.0070552

Cited by 19 publications

(30 citation statements)

References 42 publications

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“…The VP1 protein was chosen as a target for this study, as it is the largest and most surface-exposed capsid protein that is known to elicit very high antibody titers that would require T-cell help (14,15). This structural protein is critically involved in viruscell attachment (16) and has a prime function in cellular infection.…”

Section: Donorsmentioning

confidence: 99%

“…Entire VP1 capsid proteins of the same two RV-A and -C genotypes tested in the T-cell proliferation assay (A34 and C3) were produced in our laboratory as fusion polypeptides with glutathione S-transferase (GST) at the N terminus and a hexahistidine tag on the C terminus and expressed as recombinant proteins in Escherichia coli, as previously described (14). VP1 proteins were purified by glutathione-agarose affinity chromatography (Sigma-Aldrich, St. Louis, MO) and high-resolution size exclusion chromatography (GE Healthcare, Uppsala, Sweden).…”

Section: Donorsmentioning

confidence: 99%

“…Total and species-specific antibody titers to RV-A (A34) and RV-C (C3) were measured in the plasma of all 20 donors using a dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA; PerkinElmer). The details of the technique were described previously (14). Briefly, plasma was diluted (1:100) in blocking buffer (0.5% bovine serum albumin in 50 mM Tris-HCl, 0.9% NaCl, 0.05% sodium azide buffer with 0.01% Tween 20) and incubated overnight at 4°C with shaking.…”

Section: Donorsmentioning

confidence: 99%

“…Species-specific IgG1 antibody binding to RV-A and RV-C. Immunoabsorption assays were conducted as described above, except that prior to starting, each plasma was preincubated in a lysate mixture of E. coli (1:250) producing the other two RV species to absorb out cross-reactive binding, as validated previously (14). Plasma from all the donors was also preabsorbed with the irrelevant antigen PspC, a surface protein of Streptococcus pneumoniae, in order to control for nonspecific inhibition.…”

Section: Donorsmentioning

confidence: 99%

“…While the antibodies that bound the RV-C antigen were almost entirely, or often completely, cross-reactive with RV-A, there were high titers of anti-RV-A antibodies that did not cross-react with RV-C or other enteroviruses (14,15). This pattern was found in both healthy and asthmatic subjects, including asthmatic children admitted to the hospital following a recent RV-C infection (15).…”

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confidence: 91%

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Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Gaido

Stone

Chopra

et al. 2016

J Virol

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Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide, and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune responses to the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors. Human leukocyte antigen (HLA) was typed in all the donors in order to investigate possible associations between the HLA type and RV peptide recognition. Total and specific IgG1 antibody titers to the VP1 proteins of both RV-A and RV-C were also measured to examine associations between the antibody and T-cell responses. We identified T-cell epitopes that are specific to and representative of each RV-A and RV-C species. These epitopes stimulated CD4 ؉ -specific T-cell proliferation, with similar magnitudes of response for both RV species. All the donors, independent of their HLA-DR or -DQ type, were able to recognize the immunodominant RV-A and -C regions of VP1. Furthermore, the presence or absence of specific antibody titers was not related to changes in T-cell recognition. Our results indicate a dissociation between the antibody and T-cell responses to rhinoviruses. The species-representative T-cell epitopes identified in this study are valuable tools for future studies investigating T-cell responses to the different RV species. IMPORTANCERhinoviruses (RVs) are mostly associated with the common cold and asthma exacerbations, although their contributions to most upper and lower respiratory tract diseases have increasingly been reported. Species C (RV-C) has been associated with more frequent and severe asthma exacerbations in young children and, along with RV-A, is the most clinically relevant species. Little is known about how our immune system responds to rhinoviruses, and there are limited tools to study specific adaptive immunity against each rhinovirus species. In this study, we identified immunodominant T-cell epitopes of the VP1 proteins of RV-A and RV-C, which are representative of each species. The study found that T-cell responses to RV-A and RV-C were of similar magnitudes, in contrast with previous findings showing RV-C-specific antibody responses were low. These findings will provide the basis for future studies on the immune response to rhinoviruses and can help elucidate the mechanisms of severity of rhinovirus-induced infections.

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Section: Donorsmentioning

confidence: 99%

Section: Donorsmentioning

confidence: 99%

Section: Donorsmentioning

confidence: 99%

Section: Donorsmentioning

confidence: 99%

mentioning

confidence: 91%

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Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Gaido

Stone

Chopra

et al. 2016

J Virol

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Influenza‐specific IgG1⁺ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency

et al. 2020

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Background. Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen-specific response. Objective. To quantify and characterise the antigen-specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. Methods. Recombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells. Results. Recombinant HA tetramers were specifically recognised by 0.5-1% of B cells in previously vaccinated healthy adults. HA-specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HAspecific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination. Conclusion. We have successfully identified AM15-specific Bmem cells in healthy controls and PAD patients. The presence of antigen-specific Bmem cells could offer

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Rhinoviruses A and C elicit long‐lasting antibody responses with limited cross‐neutralization

Bochkov,

Devries,

Tetreault

et al. 2023

Journal of Medical Virology

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Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross‐neutralization. We previously showed that neutralizing antibody (nAb) responses to RV‐C are detected twofold to threefold more often than those to RV‐A throughout childhood. Based on those findings, we hypothesized that RV‐C infections are more likely to induce either cross‐neutralizing or longer‐lasting antibody responses compared with RV‐A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV‐A or RV‐C types using log‐linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV‐A versus RV‐C nAb responses. Our models identified limited reciprocal cross‐neutralizing relationships for RV‐A (A12–A75, A12–A78, A20–A78, and A75–A78) and only one for RV‐C (C2–C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV‐C2. Mixed‐effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV‐A and RV‐C illnesses induced nAb responses of similar duration. These results indicate that both RV‐A and RV‐C nAb responses have only modest cross‐reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV‐C species may include even fewer cross‐neutralizing types than RV‐A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.

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Species-Specific and Cross-Reactive IgG1 Antibody Binding to Viral Capsid Protein 1 (VP1) Antigens of Human Rhinovirus Species A, B and C

Cited by 19 publications

References 42 publications

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Influenza‐specific IgG1⁺ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency

Rhinoviruses A and C elicit long‐lasting antibody responses with limited cross‐neutralization

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Species-Specific and Cross-Reactive IgG1 Antibody Binding to Viral Capsid Protein 1 (VP1) Antigens of Human Rhinovirus Species A, B and C

Cited by 19 publications

References 42 publications

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency

Rhinoviruses A and C elicit long‐lasting antibody responses with limited cross‐neutralization

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Influenza‐specific IgG1⁺ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency