Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

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.

Complete Genome Sequence of a Zika Virus Strain Isolated from the Serum of an Infected Patient in Thailand in 2006.

The complete genome of Zika virus (ZIKV) strain CVD_06-274 was isolated from the serum of an infected patient in Thailand in 2006. Phylogenetic analysis showed that this strain belongs to the Asian lineage and also high titers in Vero cells (RCB 10-87). It has potential for development as an inactivated ZIKV vaccine.

Process optimization for an industrial-scale production of Diphtheria toxin by Corynebacterium diphtheriae PW8.

In this study, several parameters affecting the toxin production of Corynebacterium diphtheriae Parke Williams 8 (PW8) were investigated in detail. The comparison studies of amino acid profile in NZ Amine A-based medium (NZ medium) and beef digest-based medium (BD medium) suggested that an insufficient supply of amino acids was not responsible for low toxin yield observed in NZ medium. Supplementation of additional amino acids and growth promoting nutrient (in a form of yeast extract) into NZ medium enhanced only cell growth but not toxin production. Thus, BD medium was selected as the most suitable base medium for toxin production as it gave a significantly higher limit of flocculation (93 ± 0 Lf/ml) than NZ medium (46 ± 0 Lf/ml). Interestingly, a supplementation of 0.2% YE into BD medium resulted in a significant increase in growth as well as toxin production (235 ± 5 Lf/ml). In conclusion, consistently high toxin titer (174-239 Lf/ml) could be obtained from BD medium at a 5 L-scale production as long as 1) the protein content of BD medium was at least 24 g/L, 2) the iron content was below 0.15 ppm and 3) 0.2% YE was supplemented into the medium.

Characterization of schwann cells in self-assembled sheets from thermoresponsive substrates.

Schwann cells are the vital glial cells in the development and regeneration of the peripheral nervous system (PNS). Recently, Schwann cell transplantation has emerged as one of the attractive candidates in treating demyelinating diseases resulting from the PNS and central nervous system injuries. Schwann cells are usually injected as cell suspensions or transplanted after being seeded on extracellular matrix proteins or biodegradable polymeric scaffolds. In these approaches, the adherens junctions between Schwann cells present in vivo are not readily replicated as Schwann cells dispersed as individual cells. Here we describe a procedure to grow a large amount of Schwann cells in a sheet architecture that can be either transplanted or injected and provide some insights into the influence of a sheet-like cell organization on the function of Schwann cells, including their viability, proliferation, alignment, and migration. The Schwann cell sheet was successfully generated through coating the culture plate surfaces by layer-by-layer self-assembly of the thermoresponsive polymer poly-(N-isopropylacrylamide) (PNIPAAM). Further characterization of the Schwann cell sheet showed that Schwann cells in sheet were highly viable, but maintained a lower proliferation rate than individual Schwann cells. The levels of nerve growth factor and glial cell-derived neurotrophic factor were also maintained in Schwann cell sheets. The protein level of a cyclin-dependent kinase inhibitor, p27, was upregulated in the Schwann cell sheet. Both alignment with axon-like nanofibers and migration of Schwann cells are not significantly different between Schwann cells in a sheet-like organization and as individual cells. We conclude that Schwann cell sheet engineering presents a promising method for cell-based nerve injury therapy, as well as a model to study the control of Schwann cell proliferation in response to intercellular organization.