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10.1038/s41586-021-03673-2 http://scihub22266oqcxt.onion/10.1038/s41586-021-03673-2 34082438!8742224!34082438     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2021 ; 595 (7869): 718-723 Nephropedia Template TP {{tp|p=34082438|t=2021. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants |pdf=|usr=}}{{34082438}} gab.com Text Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=34082438 #FOAvip Resistance represents a major challenge for antibody-based therapy for COVID-19(1-4). Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19. Twit Text FOAVip Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=34082438 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34082438 #FOAvip English Wikipedia <ref>{{Cite pmid|34082438}}</ref> Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants #MMPMID34082438 Ku Z; Xie X; Hinton PR; Liu X; Ye X; Muruato AE; Ng DC; Biswas S; Zou J; Liu Y; Pandya D; Menachery VD; Rahman S; Cao YA; Deng H; Xiong W; Carlin KB; Liu J; Su H; Haanes EJ; Keyt BA; Zhang N; Carroll SF; Shi PY; An Z Nature 2021[Jul]; 595 (7869): 718-723 PMID34082438show ga Resistance represents a major challenge for antibody-based therapy for COVID-19(1-4). Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19. |Administration, Intranasal[MESH] |Angiotensin-Converting Enzyme 2/antagonists & inhibitors/metabolism[MESH] |Animals[MESH] |Antibodies, Monoclonal/adverse effects/genetics/immunology/pharmacokinetics[MESH] |Antibodies, Neutralizing/administration & dosage/adverse effects/genetics/immunology[MESH] |Apoptosis Regulatory Proteins/chemistry/genetics/immunology/metabolism[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/immunology/*prevention & control/*virology[MESH] |Dose-Response Relationship, Immunologic[MESH] |Female[MESH] |Humans[MESH] |Immunoglobulin A/genetics/immunology[MESH] |Immunoglobulin G/immunology[MESH] |Immunoglobulin M/*administration & dosage/adverse effects/*immunology/therapeutic use[MESH] |Mice[MESH] |Mice, Inbred BALB C[MESH] |Protein Engineering[MESH] |Receptors, Virus/antagonists & inhibitors/metabolism[MESH]Nasal delivery of an IgM offers broad protection from SARS-CoV-2 varia(epmc).pdf DeepDyve Pubget Overpricing