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Publications (7 of 7) Show all publications
Vikström, L., Fjällström, P., Gwon, Y.-D., Sheward, D. J., Wigren-Byström, J., Evander, M., . . . Forsell, M. N. E. (2023). Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study. The Lancet Regional Health: Europe, 30, Article ID 100646.
Open this publication in new window or tab >>Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study
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2023 (English)In: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 30, article id 100646Article in journal (Refereed) Published
Abstract [en]

Background: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.

Methods: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.

Findings: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG.

Interpretation: In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Correlate of protection, COVID-19, Immune monitoring of vulnerable populations, Longevity of vaccination, Open cohort study, Vaccination, Vulnerable population
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-208263 (URN)10.1016/j.lanepe.2023.100646 (DOI)2-s2.0-85156247971 (Scopus ID)
Funder
Swedish Research CouncilScience for Life Laboratory, SciLifeLabKnut and Alice Wallenberg FoundationVinnovaSwedish Association of Local Authorities and RegionsFamiljen Erling-Perssons Stiftelse
Available from: 2023-05-24 Created: 2023-05-24 Last updated: 2023-07-14Bibliographically approved
Masika, M. M., Korhonen, E. M., Smura, T., Uusitalo, R., Ogola, J., Mwaengo, D., . . . Huhtamo, E. (2022). Serological Evidence of Exposure to Onyong-Nyong and Chikungunya Viruses in Febrile Patients of Rural Taita-Taveta County and Urban Kibera Informal Settlement in Nairobi, Kenya. Viruses, 14(6), Article ID 1286.
Open this publication in new window or tab >>Serological Evidence of Exposure to Onyong-Nyong and Chikungunya Viruses in Febrile Patients of Rural Taita-Taveta County and Urban Kibera Informal Settlement in Nairobi, Kenya
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2022 (English)In: Viruses, E-ISSN 1999-4915, Vol. 14, no 6, article id 1286Article in journal (Refereed) Published
Abstract [en]

Several alphaviruses, such as chikungunya (CHIKV) and Onyong-nyong (ONNV), are endemic in Kenya and often cause outbreaks in different parts of the country. We assessed the seroprevalence of alphaviruses in patients with acute febrile illness in two geographically distant areas in Kenya with no previous record of alphavirus outbreaks. Blood samples were collected from febrile patients in health facilities located in the rural Taita-Taveta County in 2016 and urban Kibera informal settlement in Nairobi in 2017 and tested for CHIKV IgG and IgM antibodies using an in-house immunofluorescence assay (IFA) and a commercial ELISA test, respectively. A subset of CHIKV IgG or IgM antibody-positive samples were further analyzed using plaque reduction neutralization tests (PRNT) for CHIKV, ONNV, and Sindbis virus. Out of 537 patients, 4 (0.7%) and 28 (5.2%) had alphavirus IgM and IgG antibodies, respectively, confirmed on PRNT. We show evidence of previous and current exposure to alphaviruses based on serological testing in areas with no recorded history of outbreaks.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
alphavirus, arbovirus, chikungunya, ELISA, febrile illness, immunofluorescence, neutralization, Onyong-nyong, seroprevalence
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-203180 (URN)10.3390/v14061286 (DOI)000818334100001 ()35746757 (PubMedID)2-s2.0-85132365824 (Scopus ID)
Funder
Academy of Finland
Available from: 2023-01-16 Created: 2023-01-16 Last updated: 2024-01-17Bibliographically approved
Normark, J., Vikström, L., Yong-Dae, G., Persson, I.-L., Edin, A., Björsell, T., . . . Forsell, M. N. E. (2021). Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination [Letter to the editor]. New England Journal of Medicine, 385(11), 1049-1051
Open this publication in new window or tab >>Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination
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2021 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 385, no 11, p. 1049-1051Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Massachusetts Medical Society, 2021
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-187330 (URN)10.1056/NEJMc2110716 (DOI)000674415300001 ()34260850 (PubMedID)2-s2.0-85111281855 (Scopus ID)
Available from: 2021-09-08 Created: 2021-09-08 Last updated: 2022-04-27Bibliographically approved
Yong-Dae, G., Mahani, S. A., Nagaev, I., Mincheva-Nilsson, L. & Evander, M. (2021). Rift valley fever virus propagates in human villous trophoblast cell lines and induces cytokine mrna responses known to provoke miscarriage. Viruses, 13(11), Article ID 2265.
Open this publication in new window or tab >>Rift valley fever virus propagates in human villous trophoblast cell lines and induces cytokine mrna responses known to provoke miscarriage
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2021 (English)In: Viruses, E-ISSN 1999-4915, Vol. 13, no 11, article id 2265Article in journal (Refereed) Published
Abstract [en]

The mosquito-borne Rift Valley fever (RVF) is a prioritised disease that has been listed by the World Health Organization for urgent research and development of counteraction. Rift Valley fever virus (RVFV) can cause a cytopathogenic effect in the infected cell and induce hyperimmune responses that contribute to pathogenesis. In livestock, the consequences of RVFV infection vary from mild symptoms to abortion. In humans, 1–3% of patients with RVFV infection develop severe disease, manifested as, for example, haemorrhagic fever, encephalitis or blindness. RVFV infection has also been associated with miscarriage in humans. During pregnancy, there should be a balance between pro-inflammatory and anti-inflammatory mediators to create a protective environment for the placenta and foetus. Many viruses are capable of penetrating that protective environment and infecting the foetal–maternal unit, possibly via the trophoblasts in the placenta, with potentially severe consequences. Whether it is the viral infection per se, the immune response, or both that contribute to the pathogenesis of miscarriage remains unknown. To investigate how RVFV could contribute to pathogenesis during pregnancy, we infected two human trophoblast cell lines, A3 and Jar, representing normal and transformed human villous trophoblasts, respectively. They were infected with two RVFV variants (wild-type RVFV and RVFV with a deleted NSs protein), and the infection kinetics and 15 different cytokines were analysed. The trophoblast cell lines were infected by both RVFV variants and infection caused upregulation of messenger RNA (mRNA) expression for interferon (IFN) types I–III and inflammatory cytokines, combined with cell linespecific mRNA expression of transforming growth factor (TGF)-β1 and interleukin (IL)-10. When comparing the two RVFV variants, we found that infection with RVFV lacking NSs function caused a hyper-IFN response and inflammatory response, while the wild-type RVFV suppressed the IFN I and inflammatory response. The induction of certain cytokines by RVFV infection could potentially lead to teratogenic effects that disrupt foetal and placental developmental pathways, leading to birth defects and other pregnancy complications, such as miscarriage.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Cytokine, Human villous trophoblast, Inflammatory cytokines, Interferon, Miscarriage, Rift valley fever virus
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-189994 (URN)10.3390/v13112265 (DOI)000725992400001 ()2-s2.0-85119521104 (Scopus ID)
Funder
Region VästerbottenSwedish Research Council, 2018-02637
Available from: 2021-11-30 Created: 2021-11-30 Last updated: 2024-01-17Bibliographically approved
Kirui, J., Abidine, Y., Lenman, A., Islam, M. K. K., Yong-Dae, G., Lasswitz, L., . . . Gerold, G. (2021). The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry. Cells, 10(7), Article ID 1828.
Open this publication in new window or tab >>The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry
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2021 (English)In: Cells, E-ISSN 2073-4409, Vol. 10, no 7, article id 1828Article in journal (Refereed) Published
Abstract [en]

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Chikungunya virus, CHIKV, alphavirus, enveloped virus, phosphatidylserine, T-cell immunoglobulin and mucin domain 1, TIM-1, Axl receptor tyrosine kinase, Axl, entry
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-187299 (URN)10.3390/cells10071828 (DOI)000676394100001 ()34359995 (PubMedID)2-s2.0-85114081934 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 2017-05607
Available from: 2021-09-09 Created: 2021-09-09 Last updated: 2021-09-09Bibliographically approved
Yong-Dae, K., Zusinaite, E., Merits, A., Överby, A. K. & Evander, M. (2020). N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle. Viruses, 12(9), Article ID 925.
Open this publication in new window or tab >>N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle
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2020 (English)In: Viruses, E-ISSN 1999-4915, Vol. 12, no 9, article id 925Article in journal (Refereed) Published
Abstract [en]

Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein areN-glycosylated. The prM protein of all ZIKV strains contains a singleN-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when theN-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found thatN-glycosylation was necessary for effective secretion of ZIKV virions. The absence of theN-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of theN-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prMN-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
Zika virus, N-glycosylation, pre-membrane, envelope, virus life cycle
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-176452 (URN)10.3390/v12090925 (DOI)000580340900001 ()32842538 (PubMedID)2-s2.0-85089933821 (Scopus ID)
Available from: 2020-11-20 Created: 2020-11-20 Last updated: 2024-01-17Bibliographically approved
Seruyange, E., Ljungberg, K., Muvunyi, C. M., Gahutu, J. B., Katare, S., Nyamusore, J., . . . Bergstrom, T. (2019). Seroreactivity to Chikungunya and West Nile Viruses in Rwandan Blood Donors. Vector Borne and Zoonotic Diseases, 19(10), 731-740
Open this publication in new window or tab >>Seroreactivity to Chikungunya and West Nile Viruses in Rwandan Blood Donors
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2019 (English)In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 19, no 10, p. 731-740Article in journal (Refereed) Published
Abstract [en]

Introduction: Chikungunya virus (CHIKV) and West Nile virus (WNV) have previously been reported from several African countries, including those bordering Rwanda where they may have originated. However, there have been no serosurveillance reports from Rwanda regarding these two viral pathogens. In this article, we present the first study of immunoglobulin G (IgG) seroreactivity of CHIKV and WNV in Rwandan blood donor samples. Methods: Blood donors from Rwanda (n = 874) and Sweden (n = 199) were tested for IgG reactivity against CHIKV, using an in-house enzyme-linked immunosorbent assay with the E1 envelope protein fused with p62 as antigen, and against WNV using a commercial kit. Data on mosquito distribution were obtained from the 2012 assessment of yellow fever virus circulation in Rwanda. Results: Seroreactivity to CHIKV was high in Rwanda (63.0%), when compared with Swedish donors, where only 8.5% were IgG positive. However, a cross-reactivity to O'nyong'nyong virus in neutralization test was noted in Rwandan donors. No significant difference in WNV seroreactivity was found (10.4% for Rwandan and 14.1% for Swedish donors). The relatively high seroreactivity to WNV among Swedish donors could partly be explained by cross-reactivity with tick-borne encephalitis virus prevalent in Sweden. Donors from the Eastern Province of Rwanda had the highest IgG reactivity to the two investigated viruses (86.7% for CHIKV and 33.3% for WNV). Five genera of mosquitoes were found in Rwanda where Culex was the most common (82.5%). The vector of CHIKV, Aedes, accounted for 9.6% of mosquitoes and this species was most commonly found in the Eastern Province. Conclusions: Our results showed high seroreactivity to CHIKV in Rwandan donors. The highest IgG reactivity to CHIKV, and to WNV, was found in the Eastern Province, the area reporting the highest number of mosquito vectors for these two viruses. Infection control by eliminating mosquito-breeding sites in population-dense areas is recommended, especially in eastern Rwanda.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2019
Keywords
seroreactivity, chikungunya virus, West Nile virus, ELISA, mosquitoes, Rwanda
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-164450 (URN)10.1089/vbz.2018.2393 (DOI)000488806000004 ()31246538 (PubMedID)2-s2.0-85072904866 (Scopus ID)
Available from: 2019-10-22 Created: 2019-10-22 Last updated: 2023-03-23Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0703-4188

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