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Cross-reactive immune responses in mice after genetic vaccination with cDNA encoding hantavirus nucleocapsid proteins.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
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2007 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 25, no 9, 1690-1699 p.Article in journal (Refereed) Published
Abstract [en]

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in about 150,000 individuals in Eurasia, and several hundred cases of hantavirus pulmonary syndrome (HPS) on the American continent annually. There is consequently a need for rapid diagnostics and effective prevention of hantaviral infections. In this study we have performed DNA-vaccination of mice with full-length genes encoding the immunogenic nucleocapsid protein (NP) of Puumala (PUUV), Seoul (SEOV) and Sin Nombre virus (SNV). The antibody reactivity towards the NPs, and deleted or truncated variants thereof, were studied to localise and investigate the major polyclonal B-cell epitopes. Our findings clearly show that the antibody reactivity in each immunised mouse is unique, not only in a quantitative respect (titers) but also in cross-reactivity and most likely also in the epitope specificity. Our experimental data in combination with B-cell prediction software indicate that strong homologous virus species specific and cross-reactive epitopes are located around amino acid residue 40 in the nucleocapsid proteins.

Place, publisher, year, edition, pages
2007. Vol. 25, no 9, 1690-1699 p.
National Category
Infectious Medicine
URN: urn:nbn:se:umu:diva-22245DOI: 10.1016/j.vaccine.2006.09.082PubMedID: 17110000OAI: diva2:214131
Available from: 2009-05-04 Created: 2009-05-04 Last updated: 2015-07-03
In thesis
1. Genetic and serologic characterization of a Swedish human hantavirus isolate
Open this publication in new window or tab >>Genetic and serologic characterization of a Swedish human hantavirus isolate
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hantaviruses are found practically all over the world and cause hemorrhagic fevers in man. Each year about 150,000 people are hospitalized in these zoonotic infections which can be of two types: hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS), depending on the infecting virus. Hantavirus infections are emerging infectious diseases. That is, the number of reported cases of hantaviral disease is increasing, new hantaviruses are discovered continually, and already known hantaviruses are expected to spread to new areas. Therefore, knowledge and monitoring of these viruses are imperative from a public health perspective.

In this thesis, the characterization of a local human Puumala (PUUV) virus isolate is described. Genetic and serological relationships to other hantaviruses are investigated and the viral protein interactions, critical for genome packaging and assembly, are studied. We found that the nucleotide and amino acid sequences of the local PUUV strains are significantly different from the PUUV prototype strain Sotkamo, a difference that indicates that there might be a risk of misdiagnosing PUUV infected patients when using reagents derived from the prototype strain. These data contributed to the introduction of locally derived diagnostic tools to the Laboratory of Clinical Virology at the Umeå University hospital, which is the reference centre for hantaviral diseases in Sweden. Furthermore, when studying the underlying mechanisms of genome packaging, we identified several regions and amino acids absolutely required for nucleocapsid protein interactions. Also, a region that appeared to regulate this interaction was discovered. Finally, the serological immune responses in DNA-vaccinated mice and PUUV infected patients were investigated. We found that the cross-reactive antibody response in vaccinated mice and in infected individuals was unique and independent of homologous titres. Furthermore, four immunodominant epitopes with specific cross-reactive characteristics were identified.

Our findings have highlighted the complexity of the serological immune responses to hantavirus infections, and they emphasize the importance of customizing the diagnostic tools and performing clinical analyses on locally derived strains. In conclusion, we believe that these results are valuable in the development of new serological, genetic, and epidemiological tools.

Place, publisher, year, edition, pages
Umeå: Infektionssjukdomar, 2008. 72 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1204
hantavirus, puumalavirus, diagnostics, HFRS, nucleocapsid protein, B-cell epitopes, epitope-mapping, protein interactions, glycosylation, antibody response, cross-reactivity
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-1878 (URN)978-91-7264-636-0 (ISBN)
Public defence
2008-10-24, Sal D, 1D, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2008-10-10 Created: 2008-10-10 Last updated: 2009-05-04Bibliographically approved

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