Biology subjects

Mitoma, S.

Publications and source records attributed to Mitoma, S..

4 recordsLinked to original sources

bioRxiv2023

An engineered ACE2 decoy broadly neutralizes Omicron subvariants and shows therapeutic effect in SARS-CoV-2-infected cynomolgus macaques

The Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previously reported its broad spectrum and therapeutic potential in rodent models. Here, we show that engineered ACE2 decoy retains the neutralization activity against Omicron subvariants including the currently emerging XBB and BQ.1 which completely evade antibodies in clinical use. The culture of SARS-CoV-2 under suboptimal concentration of neutralizing drugs generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against engineered ACE2 decoy. As the efficient drug delivery to respiratory tract infection of SARS-CoV-2, inhalation of aerosolized decoy treated mice infected with SARS-CoV-2 at a 20-fold lower dose than the intravenous administration. Finally, engineered ACE2 decoy exhibited the therapeutic efficacy for COVID-19 in cynomolgus macaques. Collectively, these results indicate that engineered ACE2 decoy is the promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation can be considered as a non-invasive approach to enhance efficacy in the treatment of COVID-19.

microbiology↗

bioRxiv2022

Identifying Pathogen and Allele Type Simultaneously (IPATS) in a single well using droplet digital PCR

A combined host biomarker and pathogen diagnosis provides insight into disease progression risk and contributes to appropriate clinical decision-making regarding prevention and treatment. In preventive veterinary medicine, such combined diagnosis could improve risk-based livestock herd management. We developed a single-well based test for combined diagnosis of bovine leukemia virus (BLV) and bovine MHC (BoLA)-DRB3 alleles. A fourplex droplet digital PCR method targeting the BLV pol gene, BLV-susceptible DRB3*016:01 allele, resistant DRB3*009:02 allele, and housekeeping RPP30 gene (IPATS-BLV) successfully measured the percentage of BLV-infected cells and determined allele types precisely. Furthermore, it discriminated homozygous from heterozygous carriers. Using this method to determine the impact of carrying these alleles on the BLV proviral load (PVL), we found DRB3*009:02-carrying cattle could suppress the PVL to a low or undetectable level, even with the presence of a susceptible allele. Although the population of DRB3*016:01-carrying cattle showed significantly higher PVLs when compared with cattle carrying other alleles, their individual PVLs were highly variable. Because of the simplicity and speed of this single-well assay, IPATS could be a suitable platform for the combined diagnosis of host biomarkers and pathogens in a wide range of other systems.

microbiology↗

bioRxiv2022

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2. HighlightsO_LISpike L452R/Q/M mutations increase the effective reproduction number of BA.2 C_LIO_LIBA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infections C_LIO_LIBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2 C_LIO_LIBA.4/5 is more pathogenic than BA.2 in hamsters C_LI

microbiology↗

bioRxiv2018

Identification of meteorological factors affecting migration of wild birds into miyazaki and its relation to circulation of highly pathogenic avian influenza virus

Aim of our study is to establish models for predicting the number of migratory wild birds based on the meteorological data. From 136 species of wild birds, which have been observed at Futatsudate in Miyazaki, Japan, from 2008 to 2016, we selected the potential high-risk species, which can introduce highly pathogenic avian influenza (HPAI) virus into Miyazaki; we defined them as \"risky birds\". We then performed regression analysis to model the relationship between the number of risky birds and meteorological data. We selected 10 wild bird species as risky birds: Mallard (Anas platyrhynchos), Northern pintail (Anas acuta), Eurasian wigeon (Anas penelope), Eurasian teal (Anas crecca), Common pochard (Aythya ferina), Eurasian coot (Fulica atra), Northern shoveler (Anas clypeata), Common shelduck (Tadorna tadorna), Tufted duck (Aythya fuligula), and Herring gull (Larus argentatus). We succeeded in identifying five meteorological factors associated with their migration: station pressure, mean value of global solar radiation, minimum of daily maximum temperature, days with thundering, and days with daily hours of daylight under 0.1 h. We could establish some models for predicting the number of risky birds based only on the published meteorological data, without manual counting. Dynamics of migratory wild birds has relevance to the risk of HPAI outbreak, so our data could contribute to save the cost and time in strengthening preventive measures against the epidemics.

epidemiology↗