| 1. |
- Marcotte, Harold, et al.
(author)
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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages
- 2024
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In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 121:3
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Journal article (peer-reviewed)abstract
- The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previ- ously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot suffi- ciently boost the mucosal secretory IgA response in uninfected individuals, particu- larly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgAl antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibod- ies, dimeric and secretory IgAl antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgAl form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secre- tory IgA delivered by nasal administration may potentially be exploited for the treatment Iand prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.
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| 2. |
- Zhao, Peiyu, et al.
(author)
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Stable lithium metal anode enabled by high-dimensional lithium deposition through a functional organic substrate
- 2020
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In: Energy Storage Materials. - : Elsevier BV. - 2405-8297. ; 33, s. 158-163
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Journal article (peer-reviewed)abstract
- The growth of lithium dendrites severely restricts the development of lithium metal batteries. In order to achieve the goal of dendrites-free lithium in principle, it is crucial and urgent to control nucleation and growth of lithium. Here, a functional organic layer of perylene-3, 4, 9, 10-tetracarboxydiimide-lithium (PTCDI-Li) is built on the lithium anode surface by in-situ chemical reaction of PTCDI and Li metal. PTCDI-Li, with high surface energy (-10.19 eV) and low diffusion barrier (0.89 eV), efficiently promotes disk-shaped high-dimensional nucleation by regulation of lithium ion flux upon lithium plating, leading to a dendrites-free morphology. When operating under a relatively high current density of 10 mA cm−2, the Li | Li symmetrical cells with PTCDI-Li exhibit outstanding cyclic stability for 300 hours with ultralow overpotential of 400 mV, superior to the most of the reported lithium anode. The corresponding PTCDI-Li batteries show high specific capacity and enhanced cycle life. We anticipate that this strategy of regulation of lithium deposition from one-dimensional to high-dimensional opens a new horizon in the development of dendrites-free Li anodes.
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