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2. A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells

Author

Appelberg, S., Ahlén, G., Yan, J., Nikouyan, N., Weber, S., Larsson, O., Höglund, U., Aleman, S., Weber, F., Perlhamre, E., Apro, J., Gidlund, E. -K, Tuvesson, O., Salati, S., Cadossi, M., Tegel, Hanna, Hober, Sophia, Frelin, L., Mirazimi, A., Sällberg, M., Appelberg, S., Ahlén, G., Yan, J., Nikouyan, N., Weber, S., Larsson, O., Höglund, U., Aleman, S., Weber, F., Perlhamre, E., Apro, J., Gidlund, E. -K, Tuvesson, O., Salati, S., Cadossi, M., Tegel, Hanna, Hober, Sophia, Frelin, L., Mirazimi, A., and Sällberg, M.

Abstract

New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines., QC 20230523

Published
2022
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12. Synthetic peptides as mini antibodies

Author

Sällberg, M., primary, Levi, M., additional, Rudén, U., additional, Pushko, P., additional, Bichko, V., additional, Magnius, L. O., additional, Tsimanis, A., additional, and Wahren, B., additional

Published
1994
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18. Long-term follow-up of successful hepatitis C virus therapy : waning immune responses and disappearance of liver disease are consistent with cure.

Author

Hedenstierna, M, Weiland, O, Brass, A, Bankwitz, D, Behrendt, P, Uhnoo, I, Aleman, S, Cardell, Kristina, Frydén, Aril, Norkrans, G, Eilard, A, Glaumann, H, Pietschmann, T, Sällberg, M, Brenndörfer, E D, Hedenstierna, M, Weiland, O, Brass, A, Bankwitz, D, Behrendt, P, Uhnoo, I, Aleman, S, Cardell, Kristina, Frydén, Aril, Norkrans, G, Eilard, A, Glaumann, H, Pietschmann, T, Sällberg, M, and Brenndörfer, E D

Abstract

BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses. AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR. METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation. RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies. CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease., EDB was supported by grants from the Swedish Society for Medical Research, the Ruth and Richard Julin Foundation, the Professor Nanna Svartz Fund, the Ake Wiberg Foundation, the Clas Groschinsky Memorial Foundation, the Goljes Memorial Fund, the Lars Hierta Memorial Foundation, the Erik and Edith Fernstrom Foundation and from Karolinska Institutet. MS was supported by the Swedish Cancer Society, the Swedish Research Council, the Stockholm County Council and Vinnova. OW was funded by Schering-Plough and MSD. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Published
2015
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21. P763 ANALYSIS OF HCV MARKERS AND IMMUNE RESPONSES 5–20 YEARS AFTER SUCCESSFUL HCV THERAPY SUGGESTS THAT MOST PATIENTS ARE CURED

Author

Brenndörfer, E.D., primary, Hedenstierna, M., additional, Bankwitz, D., additional, Behrendt, P., additional, Brass, A., additional, Uhnoo, I., additional, Aleman, S., additional, Fryden, A., additional, Norkrans, G., additional, Eilard, A., additional, Glaumann, H., additional, Cardell, K., additional, Pietschmann, T., additional, Weiland, O., additional, and Sällberg, M., additional

Published
2014
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29. Perspectives on hepatitis B infections and the efficacy of vaccination (hepatitis B and pneumococci) in dialysis patients

Author

Almroth, Gabriel, Uhlin, F, Ekermo, Bengt, Isaksson, Barbro, Kaijser, B, Andersson, B, Hahn-Zoric, M, Sällberg, M, Almroth, Gabriel, Uhlin, F, Ekermo, Bengt, Isaksson, Barbro, Kaijser, B, Andersson, B, Hahn-Zoric, M, and Sällberg, M

Abstract

Hepatitis B is a well known problem in dialysis units. We therefore examined the historical frequency of hepatitis B carriers in our unit, our vaccination program to hepatitis B virus (HBV), the response to hepatitis B vaccine, the IgG subclass response of anti-HBs and the response and IgG subclass response to pneumococcal vaccination (another vaccine) in dialysis patients. From 1970 and onwards 23 HBV carriers were found, but no new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards.Only one of the carriers was alive by the end of 2001. In four patients liver disease(in one of them liver cirrhosis) may have been a concomitant cause of death. The antibody response to hepatitis B vaccine was significantly lower in patients than in staff. In four patients a fourth injection was cancelled due to transplantation and bad health, while such data were lacking in 8 cases. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with IgG1 as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registered in 25 out of 29 dialysis patients (in all 86 %). The IgG-subclass vaccination response to pneumococci in 28 dialysis patients was mainly IgG2 and IgG1 but also occurred in IgG3 and IgG4. Prevaccination antibody levels of the controls were higher in IgG1 and IgG2 (p< 0.01) (n=21) than in dialysis patients (n=28). Hepatitis B is nowadays a rare, but still dangerous disease in nephrology units. Dialysis patients have a reduced response to hepatitis B vaccine and vaccination schedules should be started early as some patients otherwise may not receive a fourth injection. The adequate antibody response to pneumococcal vaccination mainly due to IgG2 and IgG1 antibodies indicates that the antigen involved is important in vacci

Published
2003

36. Herpesvirus serology, aberrant specific immunoglobulin G2 and G3 subclass patterns and Gm allotypes in individuals with low levels of IgG3

Author

Linde A, Söderström R, C. I. Edvard SMITH, Sällberg M, Dahl H, Grubb R, Björkander J, and Hammarström L

Subjects
Herpesvirus 4, Human, Herpesvirus 6, Human, Immunology, chemical and pharmacologic phenomena, Herpesviridae Infections, Antibodies, Viral, complex mixtures, Immunoglobulin Isotypes, Immunoglobulin M, Immunoglobulin G, parasitic diseases, Immunology and Allergy, Humans, IgG Deficiency, Immunoglobulin Allotypes, Antigens, Viral, Research Article
Abstract

SUMMARY One objective of this study was to determine whether IgG3-deficient individuals have an increased frequency of reactivated herpesvirus infections. Serum titres to Epstein-Barr virus (EBV) and human herpesvirus-6 were examined in 10 healthy and in 10 symptomatic persons with serum IgG3 < 0·1 g/l. Atypical titres were found in 16% of the IgG3-deficient individuals. Reactivations of these viruses thus do not seem common in IgG3 deficiency. Antigen-specific IgG responses were also determined. A lowered frequency of IgG3 to an EBV-derived peptide was found only in symptomatic, IgG3-deficient individuals. Levels of IgG2 to a bacterial polysaccharide were lowered in the same group, despite normal serum levels of total IgG2. A functional IgG2 deficiency may contribute to symptoms in IgG3 deficiency. The G3(g) allotype, known to be associated with low total IgG3, dominated in IgG3-deficient persons (13/17) independently of presence or absence of symptoms. A linkage of G3(g) to the G2(n) negative allotype, associated with low IgG2, was equally common irrespective of symptoms. G3(g) and absence of G2(n) seem to be one prerequisite for most of IgG3 deficiency combined with low specific IgG2.

Published
1992

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