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- Kalamara, A., et al.
(författare)
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Determination of the Ir-193(n, 2n) reaction cross section and correction methodology for the Ir-191(n, gamma) contamination
- 2019
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Ingår i: European Physical Journal A. - : SPRINGER. - 1434-6001 .- 1434-601X. ; 55:10
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Tidskriftsartikel (refereegranskat)abstract
- The cross section of the Ir-193(n, 2n)Ir-192 reaction has been determined by means of the activation technique, relative to the Al-27(n, alpha) and Au-197(n, 2n) reference reactions cross sections, at neutron beam energies ranging from 10 to 21 MeV. The quasi-monoenergetic neutron beams were produced at the 5.5 MV Tandem T11/25 Accelerator Laboratory of NCSR "Demokritos" via the H-2(d, n) and H-3(d, n) reactions. The induced gamma-ray activity of the irradiated target and reference foils was measured with high resolution HPGe detectors. In order to correct for the contribution of the Ir-191(n, gamma)Ir-192 reaction, which is open to low energy parasitic neutrons, a recently developed analysis method was implemented and it is presented in great detail. Furthermore, cross section theoretical calculations were carried out using the EMPIRE and TALYS codes over a wide energy range.
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- Mittler, Eva, et al.
(författare)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Tidskriftsartikel (refereegranskat)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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- Mittler, Eva, et al.
(författare)
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Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
- 2023
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
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Tidskriftsartikel (refereegranskat)abstract
- Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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