Biology subjects

Kawabata, H.

Publications and source records attributed to Kawabata, H..

4 recordsLinked to original sources

bioRxiv2026

A universal plug-and-display vaccine platform for mucosal and systemic immunity using Bacillus subtilis membrane vesicles

Many bacterial species naturally secrete membrane vesicles (MVs) that mediate the intercellular transport of biomolecules, including nucleic acids, proteins, and metabolites. Beyond their native physiological roles, MVs hold considerable potential for biomedical applications. Here, we demonstrate that MVs from several Bacillus species exhibit potent intrinsic adjuvant activity, efficaciously eliciting immune responses and facilitating antigen-specific antibody production in mice. Exploiting this adjuvanticity, we engineered a highly adaptable universal vaccine platform that uses B. subtilis MVs as self-adjuvanting carriers. This system employs a modular "plug-and-display" architecture that covalently anchors recombinant antigens to the MV surface through a multi-step bioconjugation cascade. After validation of this methodology using a model antigen, we adapted the platform to target Yersinia pestis, the causative agent of plague. We formulated a Y. pestis vaccine by labeling the MV surface with a modified capsule antigen fraction 1 (mCaf1). Intranasal administration of the mCaf1-MV vaccine effectively elicited both systemic and mucosal immunity. Crucially, this vaccine conferred highly efficacious protection against a lethal Y. pestis infection in a murine model. These findings demonstrate the exceptional protective efficacy of the B. subtilis MV platform and highlight its broad potential for the rapid development of mucosal vaccines against diverse emerging pathogens.

bioengineering↗

bioRxiv2025

Candidatus Rickettsia mendelii has the smallest and most ancestral-like genome in the genus Rickettsia

Rickettsia species, which constitute obligate intracellular bacteria adapted to a host-dependent lifestyle, have traditionally been classified into four phylogenetic groups. However, the available genomes are biased toward the Typhus and Spotted Fever groups, with early-diverging Ancestral group (AG) lineages being underrepresented. Here, we isolated six Candidatus Rickettsia mendelii strains from Ixodes turdus ticks in Japan. We obtained their whole-genome sequences, including one closed genome, and found that they form a distinct lineage in the AG and have the smallest genome among the known rickettsial species. Gene tree-aware reconstruction of evolutionary events using amalgamated likelihood estimation revealed that the last common ancestor of Rickettsia had a smaller gene family size than modern species do, and Ca. R. mendelii retains the most similar genomic content to this ancestral state. Various patterns of gene gain and loss among Rickettsia lineages were also suggested, highlighting their divergent evolutionary trajectories. These findings increase our understanding of Rickettsia genome evolution.

microbiology↗

bioRxiv2024

Optimization of microRNA Target Sequence Arrangement in AAV Vectors Dramatically Enhances Specificity and Efficiency of Transgene Expression in Cortical Microglia

Microglia play a critical role in diseases such as Alzheimers and stroke, making them a significant target for therapeutic intervention. However, due to their immune functions in detecting and combating viral invasion, efficient gene delivery to microglia remains challenging. We achieved specific and efficient gene delivery to microglia using an adeno- associated virus (AAV) vector designed for this purpose. This microglia-targeting AAV vector includes the mouse microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (mIba1) promoter, green fluorescent protein (GFP), microRNA target sequences (miR.Ts), woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), and polyadenylation (polyA) signal, positioned between inverted terminal repeats. When miR.Ts were placed downstream of WPRE (between WPRE and polyA), gene expression occurred not only in microglia but also in a substantial number of neurons. However, when miR.Ts were positioned upstream of WPRE (between GFP and WPRE) or on both sides of WPRE, neuronal expression was significantly suppressed, resulting in selective GFP expression in microglia. Notably, positioning miR.Ts on both sides of WPRE achieved over 90% specificity and more than 60% efficiency in transgene expression in microglia three weeks after viral administration. This vector also enabled GCaMP expression in microglia, facilitating real-time monitoring of calcium dynamics and microglial process activity in the cortex. Additionally, intravenous administration of this vector with the blood-brain barrier-penetrant AAV-9P31 capsid variant resulted in extensive GFP expression selectively in microglia throughout the brain. These findings establish this AAV vector system as a robust tool for long-term, specific, and efficient gene expression in microglia.

neuroscience↗

bioRxiv2024

Wolbachia infection in Aedes aegypti does not affect its vectorial capacity for Dirofilaria immitis

Mosquito-borne diseases such as dengue and filariasis are a growing public health concern in endemic countries. Biological approaches, such as the trans-infection of Wolbachia pipientis in mosquitoes, are an alternative vector control strategy, especially for arthropod-borne viruses such as dengue. In the present study, the effect of Wolbachia (wMel strain) on the vectorial capacity of Aedes aegypti for Dirofilaria immitis was studied. Our results showed that Wolbachia does not affect the phenotype of mosquito survival or the prevalence, number, and molting rate of third-stage larvae in both susceptible and resistant strains of Ae. aegypti. RNA-seq analysis of Malpighian tubules at 2 days post-infection with D. immitis showed the differentially expressed genes (DEGs) with and without wMel infection. No characteristic immune-related gene expression patterns were observed among the DEGs. No significant change in the amount of Wolbachia was observed in the Ae. aegypti after D. immitis infection. Our results suggest that infection of D. immitis in Ae. aegypti populations will not interfere with Wolbachia-based vector control strategies in dengue-endemic areas where cases of D. immitis are present. This study demonstrated the veterinary medical validity of a dengue control program using Wolbachia.

microbiology↗