Abstract
Enteroviruses are a group of non-enveloped single stranded-stranded positive RNA viruses that cause illnesses both mild and severe. Polioviruses are the most well- known and studied human enteroviruses, but due to successful vaccination campaigns new cases are exceedingly rare. Enteroviruses have significant societal costs yearly as they cause common cold and asthma exacerbations. Enteroviruses have also been linked to type 1 diabetes and other autoimmune diseases. Studying the link between enteroviruses and chronic diseases is challenging. Thus, new immunological and serological tools are needed.
Recombinant proteins and monoclonal antibodies for studying enteroviruses and associated diseases were produced during this Ph.D project. The 3A6 anti- enterovirus monoclonal antibody produced in rat hybridoma cells has proven to be a good tool for directly detecting a broad range of enteroviruses. The recombinant VP1-proteins on the other hand have proven effective tools in detecting antibodies against enteroviruses to show prior enterovirus infections from serological samples. Antibody responses to enteroviruses were studied in serum samples from both mice and human subjects of different ages. Antibody responses to non-structural proteins 2A and 3C were found to be good indicators for an acute enterovirus infection, especially in adults. Cross-reactivities towards VP1 proteins from different enterovirus species were found to be less extensive in young children than adults, but the waning levels of maternal antibodies were determined to be a confounding factor in studying sera from children under 6 months of age, limiting the usefulness of serological assays for that age group. The performance of the antigens was tested in a multiplex setting that can be adapted to testing larger cohorts for antibodies against enteroviruses. This is crucial as high number of samples is often required for sufficient statistical power to show linkage between pathogens and (chronic) diseases.
Recombinant proteins and monoclonal antibodies for studying enteroviruses and associated diseases were produced during this Ph.D project. The 3A6 anti- enterovirus monoclonal antibody produced in rat hybridoma cells has proven to be a good tool for directly detecting a broad range of enteroviruses. The recombinant VP1-proteins on the other hand have proven effective tools in detecting antibodies against enteroviruses to show prior enterovirus infections from serological samples. Antibody responses to enteroviruses were studied in serum samples from both mice and human subjects of different ages. Antibody responses to non-structural proteins 2A and 3C were found to be good indicators for an acute enterovirus infection, especially in adults. Cross-reactivities towards VP1 proteins from different enterovirus species were found to be less extensive in young children than adults, but the waning levels of maternal antibodies were determined to be a confounding factor in studying sera from children under 6 months of age, limiting the usefulness of serological assays for that age group. The performance of the antigens was tested in a multiplex setting that can be adapted to testing larger cohorts for antibodies against enteroviruses. This is crucial as high number of samples is often required for sufficient statistical power to show linkage between pathogens and (chronic) diseases.
| Original language | English |
|---|---|
| Place of Publication | Tampere |
| Publisher | Tampere University |
| ISBN (Electronic) | 978-952-03-3154-2 |
| ISBN (Print) | 978-952-03-3153-5 |
| Publication status | Published - 2023 |
| Publication type | G5 Doctoral dissertation (articles) |
Publication series
| Name | Tampere University Dissertations - Tampereen yliopiston väitöskirjat |
|---|---|
| Volume | 903 |
| ISSN (Print) | 2489-9860 |
| ISSN (Electronic) | 2490-0028 |
