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- Ohlund, P, et al.
(författare)
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DNA-launched RNA replicon vaccines induce potent anti-Ebolavirus immune responses that can be further improved by a recombinant MVA boost
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 12459-
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Tidskriftsartikel (refereegranskat)abstract
- There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013–2016 West African outbreak of Ebolavirus disease spread rapidly and resulted in almost 30,000 cases and more than 11,000 deaths. However, the devastating outbreak has spurred the development of novel Ebolavirus vaccines. Here, we demonstrate that alphavirus-based DNA-launched self-replicating RNA replicon vaccines (DREP) encoding either the glycoprotein (GP) gene or co-expressing the GP and VP40 genes of Sudan or Zaire Ebolavirus are immunogenic in mice inducing both binding and neutralizing antibodies as well as CD8 T cell responses. In addition, antibodies were cross-reactive against another Ebolavirus, although the specificity was higher for the vaccination antigen. DREP vaccines were more immunogenic than recombinant MVA vaccines expressing the same Ebolavirus antigens. However, a DREP prime followed by an MVA boost immunization regimen improved vaccine immunogenicity as compared to DREP and MVA homologous prime-boost immunizations. Moreover, we show that a bivalent approach targeting both Sudan and Zaire Ebolavirus can be employed without significant loss of immunity. This opens for further investigation of a pan-Ebolavirus or even a pan-filovirus vaccine.
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- Sauk, M, et al.
(författare)
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NIPTmer: rapid k-mer-based software package for detection of fetal aneuploidies
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 5616-
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive prenatal testing (NIPT) is a recent and rapidly evolving method for detecting genetic lesions, such as aneuploidies, of a fetus. However, there is a need for faster and cheaper laboratory and analysis methods to make NIPT more widely accessible. We have developed a novel software package for detection of fetal aneuploidies from next-generation low-coverage whole genome sequencing data. Our tool – NIPTmer – is based on counting pre-defined per-chromosome sets of unique k-mers from raw sequencing data, and applying linear regression model on the counts. Additionally, the filtering process used for k-mer list creation allows one to take into account the genetic variance in a specific sample, thus reducing the source of uncertainty. The processing time of one sample is less than 10 CPU-minutes on a high-end workstation. NIPTmer was validated on a cohort of 583 NIPT samples and it correctly predicted 37 non-mosaic fetal aneuploidies. NIPTmer has the potential to reduce significantly the time and complexity of NIPT post-sequencing analysis compared to mapping-based methods. For non-commercial users the software package is freely available at http://bioinfo.ut.ee/NIPTMer/.
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