| 1. |
- Samuelsson, Ebba, 1991, et al.
(författare)
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Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity
- 2022
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Ingår i: Acs Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 8:9, s. 1883-1893
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Tidskriftsartikel (refereegranskat)abstract
- The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins.
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| 2. |
- Bagdonaite, Ieva, et al.
(författare)
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Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures.
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| 3. |
- Birindwa, Archippe M., et al.
(författare)
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Bacteria and viruses in the upper respiratory tract of Congolese children with radiologically confirmed pneumonia
- 2021
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute pneumonia remains a leading cause of death among children below 5 years of age in the Democratic Republic of the Congo (DR Congo), despite introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. Potential pathogens in the nasopharynx of hospitalised children with pneumonia have not been studied previously in DR Congo. Here we compare clinical characteristics, risk factors and nasopharyngeal occurrence of bacteria and viruses between children with severe and non-severe pneumonia. Methods Between June 2015 and June 2017, 116 children aged from 2 to 59 months hospitalised due to radiologically confirmed pneumonia at Panzi referral university hospital, Bukavu, Eastern DR Congo were included in the study and sampled from nasopharynx. A multiplex real-time PCR assay for detection of 15 different viruses and 5 bacterial species was performed and another multiplex PCR assay was used for pneumococcal serotype/serogroup determination. Results During the study period 85 (73%) of the children with radiologically confirmed pneumonia met the WHO classification criteria of severe pneumonia and 31 (27%) had non-severe pneumonia. The fatality rate was 9.5%. Almost all (87%) children were treated with antibiotics before they were hospitalised, in most cases with amoxicillin (58%) or trimethoprim-sulfamethoxazole (20%). The frequency of potential pathogens in the nasopharynx of the children was high, and any viral or bacterial nucleic acids present at high levels, irrespective of species or type, were significantly associated with severe pneumonia as compared with non-severe cases (52% versus 29%, p = 0.032). White blood cell count > 20,000/mu L and C-Reactive Protein > 75 mg/dL were associated with severe pneumonia at admission. Fatal outcome was in the multivariable analysis associated with having a congenital disease as an underlying condition. One or more pneumococcal serotypes/serogroups could be identified in 61 patients, and out of all identified serotypes 31/83 (37%) were non-PCV13 serotypes. Conclusions The occurrence of any bacteria or any viruses at high levels was associated with severe pneumonia at admission. Children with congenital disorders might need a higher attention when having symptoms of acute respiratory infection, as developed pneumonia could lead to fatal outcome.
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| 4. |
- Birindwa, Archippe M., et al.
(författare)
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Decreased number of hospitalized children with severe acute lower respiratory infection after introduction of the pneumococcal conjugate vaccine in the Eastern Democratic Republic of the Congo.
- 2020
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Ingår i: Pan African Medical Journal. - : Pan African Medical Journal. - 1937-8688. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: acute lower respiratory infections (ALRI) are a leading killer of children under five worldwide including the Democratic Republic of the Congo (DR Congo). We aimed to determine the morbidity and case fatality rate due to ALRI before and after introduction of the 13-valent pneumococcal conjugate vaccine (PVC13) in DR Congo 2013. Methods: data were collected from medical records of children with a diagnosis of ALRI, aged from 2 to 59 months, treated at four hospitals in the eastern DR Congo. Two study periods were defined; from 2010 to 2012 (before introduction of PCV13) and from 2014 to 2015 (after PCV13 introduction). Results: out of 21,478 children admitted to the hospitals during 2010-2015, 2,007 were treated for ALRI. The case fatality rate among these children was 4.9%. Death was significantly and independently associated with malnutrition, severe ALRI, congenital disease and symptoms of fatigue. Among the ALRI hospitalised children severe ALRI decreased from 31% per year to 18% per year after vaccine introduction (p = 0.0002) while the fatality rate remained unchanged between the two study periods. Following introduction of PCV13, 63% of the children diagnosed with ALRI were treated with ampicillin combined with gentamicin while 33% received ceftriaxone and gentamicin. Conclusion: three years after PCV13 introduction in the Eastern part of the DR Congo, we found a reduced risk of severe ALRI among children below five years. Broad-spectrum antibiotics were frequently used for the treatment of ALRI in the absence of any microbiological diagnostic support.
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| 5. |
- Birindwa, Archippe M., et al.
(författare)
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High bacterial and viral load in the upper respiratory tract of children in the Democratic Republic of the Congo
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 Muhandule Birindwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Respiratory pathogens including Streptococcus pneumoniae and Haemophilus influenzae, are implicated in the pathogenicity of acute lower respiratory infection (ALRI). These are also commonly found in both healthy and sick children. In this study, we describe the first data on the most frequent bacteria and viruses detected in the nasopharynx of children from the general population in the Eastern DR Congo. Methods From January 2014 to June 2015, nasopharyngeal samples from 375 children aged from 2 to 60 months attending health centres for immunisation or growth monitoring were included in the study. Multiplex real-time PCR assays were used for detection of 15 different viruses and 5 bacterial species and for determination of pneumococcal serotypes/serogroups in the nasopharyngeal secretions. Results High levels of S. pneumoniae were detected in 77% of cases, and H. influenzae in 51%. Rhinovirus and enterovirus were the most commonly found viruses, while respiratory syncytial virus (RSV) was rare (1%). Co-occurrence of both bacteria and viruses at high levels was detected in 33% of the children. The pneumococcal load was higher in those children who lived in a dwelling with an indoor kitchen area with an open fire, i.e. a kitchen with an open fire for cooking located inside the dwelling with the resultant smoke passing to the living room and/or bedrooms; this was also higher in children from rural areas as compared to children from urban areas or children not living in a dwelling with an indoor kitchen area with an open fire/not living in this type of dwelling. Immunization with 2–3 doses of PCV13 was associated with lower rates of pneumococcal detection. Half of the identified serotypes were non-PCV13 serotypes. The most common non-PCV13 serotypes/serogroups were 15BC, 10A, and 12F, while 5, 6, and 19F were the most prevalent PCV13 serotypes/serogroups. Conclusions The burden of respiratory pathogens including S. pneumoniae in Congolese children was high but relatively few children had RSV. Non-PCV13 serotypes/serogroups became predominant soon after PCV13 was introduced in DR Congo.
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| 6. |
- Elfving, Kristina, et al.
(författare)
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Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar : an observational study
- 2022
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Methods: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ( "IMCI pneumonia ") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia ". Results: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. Conclusion: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia.
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| 7. |
- Emgård, Matilda, 1984, et al.
(författare)
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Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13
- 2024
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Ingår i: FRONTIERS IN PUBLIC HEALTH. - 2296-2565. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Methods: Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. Results: The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. Discussion: We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.
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| 8. |
- Larsson, Simon B., et al.
(författare)
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Self-reported symptom severity, general health, and impairment in post-acute phases of COVID-19: retrospective cohort study of Swedish public employees
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR negative controls. During the first quarter of 2021, we conducted an online survey among public employees in West Sweden, with a valid COVID-19 test result. The survey assessed past-month severity of 28 symptoms and signs, self-rated health, the WHO Disability Assessment Schedule (WHODAS) 2.0 and illness severity at the time of test. We linked participants' responses to their SARS-CoV-2 PCR tests results. We compared COVID-19 positive and negative participants using univariable and multivariable regression analyses. Out of 56,221 invited, 14,222 (25.3%) responded, with a response rate of 50% among SARS-CoV-2 positive individuals. Analysis included 10,194 participants (86.4% women, mean age 45 years) who tested positive 4-12 weeks (N = 1425; subacute) and > 12 weeks (N = 1584; postcovid) prior to the survey, and 7185 PCR negative participants who did not believe that they had had COVID-19. Symptoms were highly prevalent in all groups, with worst symptoms in subacute phase participants, followed by postcovid phase and PCR negative participants. The most specific symptom for COVID-19 was loss of smell or taste. Both WHODAS 2.0 score and self-rated health were worst in subacute participants, and modestly worse in postcovid participants than in negative controls. Female gender, older age and acute illness severity had larger effects on self-rated health and WHODAS 2.0 score in PCR positive participants than in PCR negative. Studies with longer follow-up are needed to determine the long-term improvement after COVID-19.
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| 9. |
- Magnusson, Jesper, et al.
(författare)
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Cell-free DNA as a biomarker after lung transplantation: A proof-of-concept study
- 2022
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Ingår i: Immunity Inflammation and Disease. - : Wiley. - 2050-4527. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD. Methods: Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events. Results: All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015). Conclusions: This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.
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