Abstract
[Truncated abstract] Human rhinoviruses (HRV) are highly prevalent respiratory pathogens, which besides causing the common cold, are strongly associated with acute exacerbations of asthma. HRV infections in infancy have also been identified as a significant risk factor for the development of asthma in susceptible children. Of the three HRV species, the newly assigned HRV-C species is associated with more severe asthma exacerbations in children. Despite the clinical significance of HRV infections and asthma, little is known about the specific host immune responses to HRV in children with disease, or in the general population. The aim of this project was to use recombinant antigens to determine the sero-epidemiology of infection by different HRV species by measuring the antibody response in adults and children from the general population. In addition, the antibody binding responses by antigens of HRV-A, -B and -C were measured in children presenting to hospital with asthma exacerbations. Since children who develop asthma, especially those susceptible to exacerbations, have impaired IgG1 antibody responses to respiratory colonizing bacteria, it was hypothesised that the antibody responses to HRV antigens might also be defective in children with asthma and could contribute to disease. IgG1 antibody binding to viral capsid protein 1 (VP1) antigens from two genotypes of HRV-A, -B and -C was firstly quantitated in plasma of healthy adults. Recombinant VP1 antigens were expressed as glutathione S-transferase (GST) fusion proteins and the presence of secondary structures similar to the natural antigens was verified by circular dichroism analysis. VP1 antigens were also produced to closely related enteroviruses (human poliovirus Sabin and echovirus) as controls. High titres of IgG1 antibody were bound by the VP1 capsid proteins of HRV-A, -B and -C. A very high degree of cross-reactivity between HRV species was found, especially between HRV-A and HRV-C. Immunoabsorption, which removed cross-reactive binding to other species, revealed HRV-C specific titres were markedly and significantly lower than the HRV-A and HRV-B specific titres (p
| Original language | English |
|---|---|
| Qualification | Doctor of Philosophy |
| Publication status | Unpublished - 2013 |
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