Scientific Reports (Sep 2023)
Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers
- Thanarath Imsuwansri,
- Thitinan Jongthitinon,
- Niramon Pojdoung,
- Nuntana Meesiripan,
- Siriwan Sakarin,
- Chatikorn Boonkrai,
- Tossapon Wongtangprasert,
- Tanapati Phakham,
- Thittaya Audomsun,
- Chadaporn Attakitbancha,
- Pijitra Saelao,
- Phijitra Muanwien,
- Maoxin Tim Tian,
- Songsak Tongchusak,
- Bhrus Sangruji,
- Dhammika Leshan Wannigama,
- Chenphop Sawangmake,
- Watchareewan Rodprasert,
- Quynh Dang Le,
- Steven Dwi Purbantoro,
- Kananuch Vasuntrarak,
- Sirirat Nantavisai,
- Supakit Sirilak,
- Ballang Uppapong,
- Sompong Sapsutthipas,
- Sakalin Trisiriwanich,
- Thitiporn Somporn,
- Asmah Usoo,
- Natthakarn Mingngamsup,
- Supaporn Phumiamorn,
- Porawan Aumklad,
- Kwanputtha Arunprasert,
- Prasopchai Patrojanasophon,
- Praneet Opanasopit,
- Norapath Pesirikan,
- Ladda Nitisaporn,
- Jesada Pitchayakorn,
- Thana Narkthong,
- Bancha Mahong,
- Kumchol Chaiyo,
- Kanjana Srisutthisamphan,
- Ratchanont Viriyakitkosol,
- Songklot Aeumjaturapat,
- Anan Jongkaewwattana,
- Sakarn Bunnag,
- Trairak Pisitkun
Affiliations
- Thanarath Imsuwansri
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Thitinan Jongthitinon
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Niramon Pojdoung
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Nuntana Meesiripan
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Siriwan Sakarin
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Chatikorn Boonkrai
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Tossapon Wongtangprasert
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Tanapati Phakham
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Thittaya Audomsun
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Chadaporn Attakitbancha
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Pijitra Saelao
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Phijitra Muanwien
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Maoxin Tim Tian
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Songsak Tongchusak
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- Bhrus Sangruji
- School of Arts and Sciences, Tufts University
- Dhammika Leshan Wannigama
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University
- Chenphop Sawangmake
- Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University
- Watchareewan Rodprasert
- Faculty of Veterinary Science, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Chulalongkorn University
- Quynh Dang Le
- Faculty of Veterinary Science, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Chulalongkorn University
- Steven Dwi Purbantoro
- Faculty of Veterinary Science, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Chulalongkorn University
- Kananuch Vasuntrarak
- Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University
- Sirirat Nantavisai
- Academic Affairs, Faculty of Veterinary Science, Chulalongkorn University
- Supakit Sirilak
- Department of Medical Sciences, Ministry of Public Health
- Ballang Uppapong
- Department of Medical Sciences, Ministry of Public Health
- Sompong Sapsutthipas
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Sakalin Trisiriwanich
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Thitiporn Somporn
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Asmah Usoo
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Natthakarn Mingngamsup
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Supaporn Phumiamorn
- Department of Medical Sciences, Institute of Biological Products, Ministry of Public Health
- Porawan Aumklad
- Faculty of Pharmacy, Silpakorn University
- Kwanputtha Arunprasert
- Faculty of Pharmacy, Silpakorn University
- Prasopchai Patrojanasophon
- Faculty of Pharmacy, Silpakorn University
- Praneet Opanasopit
- Faculty of Pharmacy, Silpakorn University
- Norapath Pesirikan
- The Government Pharmaceutical Organization
- Ladda Nitisaporn
- The Government Pharmaceutical Organization
- Jesada Pitchayakorn
- The Government Pharmaceutical Organization
- Thana Narkthong
- The Government Pharmaceutical Organization
- Bancha Mahong
- The Government Pharmaceutical Organization
- Kumchol Chaiyo
- The Government Pharmaceutical Organization
- Kanjana Srisutthisamphan
- Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA)
- Ratchanont Viriyakitkosol
- Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA)
- Songklot Aeumjaturapat
- Otolaryngology Department, King Chulalongkorn Memorial Hospital
- Anan Jongkaewwattana
- Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA)
- Sakarn Bunnag
- Department of Medical Services, National Cancer Institute, Ministry of Public Health
- Trairak Pisitkun
- Faculty of Medicine, Center of Excellence in Systems Biology, Chulalongkorn University
- DOI
- https://doi.org/10.1038/s41598-023-42539-7
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 12
Abstract
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.
