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| 2. |
- Clo, E., et al.
(author)
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Characterization of the Viral O-Glycopeptidome: a Novel Tool of Relevance for Vaccine Design and Serodiagnosis
- 2012
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In: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 86:11, s. 6268-6278
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Journal article (peer-reviewed)abstract
- Viral envelope proteins mediate interactions with host cells, leading to internalization and intracellular propagation. Envelope proteins are glycosylated and are known to serve important functions in masking host immunity to viral glycoproteins. However, the viral infectious cycle in cells may also lead to aberrant glycosylation that may elicit immunity. Our knowledge of immunity to aberrant viral glycans and glycoproteins is limited, potentially due to technical limitations in identifying immunogenic glycans and glycopeptide epitopes. This work describes three different complementary methods for high-throughput screening and identification of potential immunodominant O-glycopeptide epitopes on viral envelope glycoproteins: (i) on-chip enzymatic glycosylation of scan peptides, (ii) chemical glycopeptide microarray synthesis, and (iii) a one-bead-one-compound random glycopeptide library. We used herpes simplex virus type 2 (HSV-2) as a model system and identified a simple O-glycopeptide pan-epitope, (501)PPA(GalNAc)TAPG(507), on the mature gG-2 glycoprotein that was broadly recognized by IgG antibodies in HSV-2-infected individuals but not in HSV-1-infected or noninfected individuals. Serum reactivity to the extended sialyl-T glycoform was tolerated, suggesting that self glycans can participate in immune responses. The methods presented provide new insight into viral immunity and new targets for immunodiagnostic and therapeutic measures.
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| 4. |
- Ahlström, A., et al.
(author)
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No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
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In: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
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Journal article (peer-reviewed)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
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| 5. |
- Bernson, Elin, 1987, et al.
(author)
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Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia
- 2018
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In: Cancer Immunology Research. - : American Association for Cancer Research (AACR). - 2326-6066 .- 2326-6074. ; 6:9, s. 1110-1119
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Journal article (peer-reviewed)abstract
- Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown. We assayed CMV IgG serostatus to determine past CMV infection in 81 nontransplanted AML patients who were receiving relapse-prevention immunotherapy comprising histamine dihydrochloride and low-dose interleukin-2 (HDC/IL2; NCT01347996). CMV seropositivity correlated negatively with leukemia-free and overall survival of patients receiving HDC/IL2, but did not correlate with outcomes in a contemporary control cohort. Analysis of outcome after stratification of patients based on concordant or discordant killer immunoglobulin-like receptor (KIR) and HLA genotypes implied that the negative impact of CMV seropositivity was restricted to patients lacking a ligand to inhibitory KIRs (iKIR). Previous CMV infection was also associated with fewer NK cells expressing only nonself iKIRs (NS-iKIR). We propose that CMV-driven NK cell education depletes the population of NS-iKIR NK cells, which in turn reduces the clinical benefit of relapse-preventive immunotherapy in AML.
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| 6. |
- Cano, F., et al.
(author)
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Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides
- 2000
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In: Vaccine. - 0264-410X .- 1873-2518. ; 18:24, s. 2743-2752
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Journal article (peer-reviewed)abstract
- A live bacterial vaccine-delivery system based on the food-grade bacterium Staphylococcus carnosus was used for delivery of peptides from the G glycoprotein of human respiratory syncytial virus, subtype A (RSV-A). Three peptides, corresponding to the G protein amino acids, 144-159 (denoted G5), 190-203 (G9) and 171-188 (G4 S), the latter with four cysteine residues substituted for serines, were expressed by recombinant means as surface-exposed on three different bacteria, and their surface accessibility on the bacteria was verified by fluorescence-activated cell sorting (FACS). Intranasal immunization of mice with the live recombinant staphylococci elicited significant anti-peptide as well as anti-virus serum IgG responses of balanced IgG1/IgG2a isotype profiles, and upon viral challenge with 10(5) tissue culture infectious doses(50) (TCID50), lung protection was demonstrated for approximately half of the mice in the G9 and G4 S immunization groups. To our knowledge, this is the first study in which protective immunity to a viral pathogen has been evoked using food-grade bacteria as vaccine-delivery vehicles.
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| 7. |
- Eriksson, Kristina, 1962, et al.
(author)
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Cutting Edge: Genetic Association between IFI16 Single Nucleotide Polymorphisms and Resistance to Genital Herpes Correlates with IFI16 Expression Levels and HSV-2-Induced IFN-β Expression.
- 2017
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 199:8, s. 2613-2617
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Journal article (peer-reviewed)abstract
- IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor proposed to act in the cyclic GMP-AMP synthase-stimulator of IFN genes pathway. Because mice do not have a clear ortholog of IFI16, this system is not suitable for genetic studies of IFI16. In this study, we have compared the dependency on IFI16, cyclic GMP-AMP synthase, and stimulator of IFN genes for type I IFN induction by a panel of pathogenic bacteria and DNA viruses. The IFN response induced by HSV-2 was particularly dependent on IFI16. In a cohort of patients with genital herpes and healthy controls, the minor G allele of the IFI16 single nucleotide polymorphism rs2276404 was associated with resistance to infection. Furthermore, the combination of this allele with the C allele of rs1417806 was significantly overrepresented in uninfected individuals. Cells from individuals with the protective GC haplotype expressed higher levels of IFI16 and induced more IFN-β upon HSV-2 infection. These data provide genetic evidence for a role for IFI16 in protection against genital herpes.
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| 8. |
- Follin, P, et al.
(author)
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Effective control measures limited measles outbreak after extensive nosocomial exposures in January-February 2008 in Gothenburg, Sweden.
- 2008
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In: Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin. - 1560-7917. ; 13:30, s. 1-5
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Journal article (peer-reviewed)abstract
- In January-February 2008, one imported case of measles initiated a series of exposures with around 380 nosocomial secondary contacts. Susceptible individuals were traced early and control measures were initiated that managed to limit the consequences considerably. Only four secondary cases were identified by the end of March. This minor outbreak illustrates the importance and efficiency of early control measures as well as the fact that the risk of measles outbreaks still exists in a country that has high measles, mumps, rubella vaccination coverage among children.
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| 9. |
- Herlitz, Johan, et al.
(author)
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Early identification of acute myocardial infarction and prognosis in relation to mode of transport
- 1992
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In: American Journal of Emergency Medicine. - : W.B. Saunders Co.. - 0735-6757 .- 1532-8171. ; 10:5, s. 406-412
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Journal article (peer-reviewed)abstract
- Of 2,840 consecutive patients who were admitted to the emergency department of a Swedish university hospital due to suspected acute myocardial infarction (AMI), only 25% were reached by the mobile coronary care unit (MCCU), and only 4% simultaneously fulfilled traditional criteria for prehospital thrombolysis (ie, had ST-segment elevation on admission electrocardiogram and a delay time of less than 6 hours). In the subset of patients who fulfilled criteria for a confirmed AMI, 31% were reached by an MCCU and 11% fulfilled criteria for prehospital thrombolysis. Among patients with confirmed AMI, the hospital mortality rate was highest in patients transported by standard ambulance (19%) versus 15% in those transported by an MCCU and 8% in those transported by other means. The authors conclude that AMI patients transported by ambulance are high-risk patients for early death. Prehospital thrombolysis might reduce their rate of mortality. However, according to the authors' experience only a minor fraction of patients are available for prehospital thrombolysis.
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| 10. |
- Jonasson, P., et al.
(author)
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Genetic design for facilitated production and recovery of recombinant proteins in Escherichia coli
- 2002
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In: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 35, s. 91-105
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Research review (peer-reviewed)abstract
- Genetic strategies have been used for more than two decades to improve bacterial bioprocesses and to simplify recovery procedures. Such strategies include the design of efficient expression vectors and the improvement of bacterial production strains in different ways, e.g. by deletion of protease genes or engineering for overexpression of rare-codon tRNAs, foldases or chaperones. Gene multimerization is another such principle that has proved beneficial to improve production yields. Genetic strategies have furthermore been exploited to facilitate recovery processes by adapting the product for a particular purification principle. In this area, affinity fusions have been commonly used, but other principles, such as modified isoelectric point (pI) or hydrophobic properties have also been successfully investigated. A recent drastic step forward in the use of gene technology to improve recovery processes for recombinant proteins is the introduction of combinatorial protein engineering to generate tailor-made product-specific affinity ligands. This strategy, which allows efficient recovery of a recombinant protein in its native form, is likely to be increasingly used also in industrial-scale bioprocesses, since novel protein ligands have been described that can be sanitized using common industrial cleaning-in-p lace procedures. The examples presented in this review make it evident that genetic strategies will be of utmost importance in the future for facilitating production and recovery of recombinant proteins.
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