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- Garcia-Ayllon, M. S., et al.
(författare)
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Plasma ACE2 species are differentially altered in COVID-19 patients
- 2021
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Ingår i: FASEB Journal. - 0892-6638. ; 35:8
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Tidskriftsartikel (refereegranskat)abstract
- Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.
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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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