| 1. |
- Ljungars, Anne, et al.
(författare)
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A bispecific IgG format containing four independent antigen binding sites
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the variable light (VL) domain in a conventional IgG. VH domains, binding several different types of antigens, were discovered and could be rearranged in any combination, offering a convenient "plug and play" format. The tetra-VH IgGs were found to be functionally tetravalent, binding two antigens on each arm of the IgG molecule simultaneously. This offers a new strategy to also create monospecific, tetravalent IgGs that, depending on antigen architecture and mode-of-action, may have enhanced efficacy compared to traditional bivalent antibodies.
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| 2. |
- Sobko, Tanja, et al.
(författare)
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Neonatal sepsis, antibiotic therapy and later risk of asthma and allergy
- 2010
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 24:1, s. 88-92
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Tidskriftsartikel (refereegranskat)abstract
- P>Sobko T, Schiott J, Ehlin A, Lundberg J, Montgomery S, Norman M. Neonatal sepsis, antibiotic therapy and later risk of asthma and allergy. Paediatric and Perinatal Epidemiology 2010; 24: 88-92. Neonatal sepsis and early antibiotic therapy affect bacterial colonisation and immune activation after birth. This could have implications for later risk of allergy and asthma. Using a validated questionnaire (International Study of Asthma and Allergies in Children, ISAAC), we screened for asthma and allergy in three cohorts (total n = 834; median age 12, range 7-23 years) with different perinatal exposures as regards infection and antibiotics. Asthma, but not hay fever, was more prevalent after neonatal sepsis with adjusted odds ratio (OR) 1.63 [95% confidence interval (CI) 1.04, 2.56] and early antibiotic therapy (OR 1.48 [0.93, 2.35]) as compared with a control group. There was a trend towards increased atopic eczema after neonatal sepsis (OR = 1.39 [CI = 0.98, 1.98]). We conclude that neonatal sepsis is associated with an increased risk for later development of asthma. Early antibiotic exposure may contribute to this association.
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