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1.
Sci Rep ; 13(1): 15648, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37730833

ABSTRACT

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.


Subject(s)
COVID-19 , Nasal Sprays , Humans , Animals , Rats , Administration, Intranasal , Immunoglobulin G , Antibodies, Neutralizing , SARS-CoV-2 , Healthy Volunteers , Antibodies, Viral
2.
PLoS One ; 18(5): e0284173, 2023.
Article in English | MEDLINE | ID: mdl-37141227

ABSTRACT

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest healthcare issue worldwide. This study aimed to develop a monoclonal antibody against SARS-CoV-2 from B cells of recovered COVID-19 patients, which might have beneficial therapeutic purposes for COVID-19 patients. We successfully generated human monoclonal antibodies (hmAbs) against the receptor binding domain (RBD) protein of SARS-CoV-2 using developed hybridoma technology. The isolated hmAbs against the RBD protein (wild-type) showed high binding activity and neutralized the interaction between the RBD and the cellular receptor angiotensin-converting enzyme 2 (ACE2) protein. Epitope binning and crystallography results displayed target epitopes of these antibodies in distinct regions beneficial in the mix as a cocktail. The 3D2 binds to conserved epitopes among multi-variants. Pseudovirion-based neutralization results revealed that the antibody cocktail, 1D1 and 3D2, showed high potency in multiple variants of SARS-CoV-2 infection. In vivo studies showed the ability of the antibody cocktail treatment (intraperitoneal (i.p.) administration) to reduce viral load (Beta variant) in blood and various tissues. While the antibody cocktail treatment (intranasal (i.n.) administration) could not significantly reduce the viral load in nasal turbinate and lung tissue, it could reduce the viral load in blood, kidney, and brain tissue. These findings revealed that the efficacy of the antibody cocktail, 1D1 and 3D2, should be further studied in animal models in terms of timing of administration, optimal dose, and efficacy to mitigate inflammation in targeted tissue such as nasal turbinate and lung.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Antibodies, Neutralizing , Antibodies, Viral/therapeutic use , Antibodies, Monoclonal , Epitopes , Spike Glycoprotein, Coronavirus
3.
Sci Rep ; 12(1): 17792, 2022 10 22.
Article in English | MEDLINE | ID: mdl-36273231

ABSTRACT

Programmed cell death protein 1 (PD-1) plays a significant role in suppressing antitumor immune responses. Cancer treatment with immune checkpoint inhibitors (ICIs) targeting PD-1 has been approved to treat numerous cancers and is the backbone of cancer immunotherapy. Anti-PD-1 molecule is necessary for next-generation cancer immunotherapy to further improve clinical efficacy and safety as well as integrate into novel treatment combinations or platforms. We developed a highly efficient hybridoma generation and screening strategy to generate high-potency chimeric anti-PD-1 molecules. Using this strategy, we successfully generated several mouse hybridoma and mouse/human chimeric clones that produced high-affinity antibodies against human PD-1 with high-quality in vitro PD-1/PD-L1 binding blockade and T cell activation activities. The lead chimeric prototypes exhibited overall in vitro performance comparable to commercially available anti-PD-1 antibodies and could be qualified as promising therapeutic candidates for further development toward immuno-oncology applications.


Subject(s)
Neoplasms , Programmed Cell Death 1 Receptor , Humans , Mice , Animals , Programmed Cell Death 1 Receptor/metabolism , B7-H1 Antigen/metabolism , Immune Checkpoint Inhibitors , Hybridomas , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/drug therapy
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