Biology subjects

Itoh, N.

Publications and source records attributed to Itoh, N..

5 recordsLinked to original sources

bioRxiv2025

Humoral immunity induced by XEC monovalent vaccines against SARS-CoV-2 variants including XEC, LP.8.1, NB.1.8.1, XFG, and BA.3.2

After the emergence of SARS-CoV-2 Omicron variant at the end of 2021, Omicron has highly diverged into various sublineages: e.g., BA.5 in 2022, XBB.1.5 in 2023, JN.1 in 2024. Currently, several JN.1 subvariants including XEC, LP.8.1, NB.1.8.1 and XFG are circulating worldwide. Additionally, recent studies show that BA.3.2, a descendant of Omicron BA.3, exhibits profound immune evasion potential. On December 5, 2025, BA.3.2, was designated a variant under monitoring by the WHO. To prevent COVID-19, several countries including Japan have continuously developed and approved variant-adapted vaccines: e.g., ancestral/BA.5 bivalent vaccine in 20223, XBB.1.5-based monovalent vaccine in 20234, JN.1-based monovalent vaccine in 2024, and LP.8.1-based monovalent vaccine in 2025. Since XEC was more prevalent than LP.8.1 at the beginning of 2025 in Japan, two Japanese pharmaceutical companies, Daiichi Sankyo and Meiji Seika Pharma, have produced XEC-based vaccines. Here, we investigated the antiviral immunity induced by XEC-based monovalent vaccines against recently circulating SARS-CoV-2 variants, as well as BA.3.2, in the Japanese population. To assess the neutralizing antibody response induced by XEC-based vaccines, we obtained sera from individuals who had been vaccinated with the XEC-based mRNA monovalent vaccine produced by Daiichi Sankyo (N=22) or the XEC-based self-amplifying replicon vaccine produced by Meiji Seika Pharma (N=20). We collected sera before and 3-4 weeks after vaccination and then performed a neutralization assay using these sera with lentivirus-based pseudoviruses harboring spike proteins of B.1.1, BA.5, XBB.1.5, JN.1, XEC, LP.8.1, NB.1.8.1, XFG and BA.3.2. The 50% neutralization titers of the sera against all variants tested were significantly increased in after vaccination in both Daiichi Sankyo cohort (2.1-fold to 11.9-fold, P<0.0001) and Meiji Seika Pharma cohort (1.4-fold to 3.9-fold, P<0.0005). Consistent with our recent study using the sera from LP.8.1-based vaccinees, the humoral immunity induced by XEC-based vaccines against JN.1 and its subvariants (XEC, LP.8.1, NB.1.8.1 and XFG) was greater than that against other variants (B.1.1, BA.5, XBB.1.5 and BA.3.2). Notably, our result showed that the XEC-based mRNA vaccine induces a stronger humoral immunity compared to the XEC-based replicon vaccine, and even the LP.8.1-adapted vaccines. However, it should be noted that our cohorts are relatively small and may include confounding factors that affect the results, such as age, sex, history of natural infection and vaccination status. Future investigations with larger cohorts are required to better understand this possibility. To compare the immune status induced by XEC- and LP.8.1-based vaccines, we analyzed the cross-neutralization induced by these vaccines using antigenic cartography. The antigenic map was depicted based on the 50% neutralization titers values obtained from this study and our recent study using LP.8.1-based vaccine sera. The cartography showed that the immune status induced by XEC-based vaccines was similar to that induced by LP.8.1-based vaccines against the nine SARS-CoV-2 variant antigens tested. In sum, our investigations, including the recent one8, suggest that all 4 of the JN.1 subvariants-based vaccines that we tested induce profound humoral immunity against a broad range of SARS-CoV-2 variants.

microbiology↗

bioRxiv2025

Humoral immunity induced by LP.8.1 monovalent vaccines against a broad range of SARS-CoV-2 variants including XEC, NB.1.8.1, XFG, and BA.3.2

In the spring of 2025, multiple SARS-CoV-2 Omicron JN.1 subvariants were circulating, with LP.8.1 among the major variants. Pharmaceutical companies such as Pfizer/BioNTech, Moderna, and Novavax/Takeda adopted monovalent LP.8.1 for their 2025-2026 season vaccines, following recommendations issued by the WHO in May 2025. As of November 2025, SARS-CoV-2 variants including LP.8.1, XEC, NB.1.8.1, and XFG--all designated as variants under monitoring--were circulating. In terms of the spike gene, these recent variants as well as LP.8.1 are derived from JN.1. Moreover, BA.3.2, a BA.3 descendant with multiple mutations in the spike gene, has recently emerged and exhibits robust immune evasion. In Japan, the rollout of the LP.8.1-based vaccination has progressed since the end of September 2025. We previously reported the humoral immunity induced by the XBB.1.5-based monovalent vaccine in 2023 and the JN.1-based monovalent vaccine in 2024 in the Japanese population. Here, we investigated the efficiency of humoral immunity induced by two LP.8.1-based vaccines, the mRNA vaccine from Pfizer/BioNTech and the recombinant protein-based vaccine from Novavax/Takeda, in Japan. We performed neutralization assays using sera obtained from individuals who received the LP.8.1 mRNA vaccine from Pfizer/BioNTech (N=29) or the LP.8.1 recombinant protein vaccine from Novavax/Takeda (N=20) with pseudoviruses harboring spike proteins of B.1.1, BA.5, XBB.1.5, JN.1, LP.8.1, XEC, NB.1.8.1, XFG and BA.3.2. In both mRNA and protein-based vaccinee groups, the change in 50% neutralizing titer (NT50) against variants that were predominant before JN.1 (i.e., B.1.1, BA.5 and XBB.1.5) were smaller than those against JN.1 and its subvariants, including LP.8.1, XEC, NB.1.8.1 and XFG. Consistent with recent studies, neutralizing antibodies against BA.3.2 were induced by both vaccines. However, the induction fold change of BA.3.2 was smaller than those of JN.1 and its subvariants. Next, we tested humoral immune response of participants who received both JN.1-based vaccine in 2024 and LP.8.1-based vaccine in 2025 (N=15). Approximately a year after the JN.1-based vaccination, neutralization titer has waned against all variants tested. However, when we compare the NT50s of pre-vaccination sera between 2025 and 2024, those in 2025 against all variants except for B.1.1 were significantly higher than those last year. This suggests that the cross-neutralizing antibodies induced by JN.1-based vaccination were still maintained for a year. Furthermore, the neutralization abilities against the JN.1 sublineages tested and BA.3.2 were significantly reboosted after the LP.8.1-based vaccination. Our study shows immune boosting by the LP.8.1-based vaccine is effective in achieving cross-neutralization against a broad range of JN.1 sublineages in a JN.1-naive population and in recalling waning humoral immunity against these subvariants.

microbiology↗

bioRxiv2025

Twinfilin-1 phosphorylation in reelin signaling regulates actin dynamics and spine development

Reelin is an extracellular glycoprotein essential for neuronal migration, spine development, and synaptic plasticity. Impaired reelin signaling is linked to neurological disorders, including schizophrenia and autism. While reelin mutant (reeler) mice exhibit behavioral deficits associated with impaired spine formation, the underlying molecular mechanisms remain unclear. We identified Twinfilin-1 (Twf1) as a downstream effector of reelin signaling via phosphoproteomic analysis, based on its reduced tyrosine phosphorylation in reeler mice. We found that Src regulated Twf1 phosphorylation at tyrosine 309, and reelin stimulation increased Twf1 phosphorylation in neurons, an effect blocked by the Src inhibitor PP2. A phospho-resistant Twf1 mutant (Twf1 Y309F) showed reduced capping protein binding and a lower F/G-actin ratio. Twf1Y309F mice exhibited cognitive deficits, reduced spine density, smaller spine head size, and a decreased F/G-actin ratio in synaptosomes. These findings highlight Twf1 phosphorylation as a key component of reelin signaling involved in actin remodeling and spine development.

neuroscience↗

bioRxiv2023

Genomic diversity of wild and cultured Yesso scallop Mizuhopecten yessoensis from Japan and Canada

The Yesso scallop Mizuhopecten yessoensis is an important aquaculture species that was introduced to Western Canada from Japan to establish an economically viable scallop farming industry. This highly fecund species has been propagated in Canadian aquaculture hatcheries for the past 40 years, raising questions about genetic diversity and genetic differences among hatchery stocks. In this study, we compare cultured Canadian and wild Japanese populations of Yesso scallop using double-digest restriction site-associated DNA (ddRAD)-sequencing to genotype 21,048 variants in 71 wild-caught scallops from Japan, 65 scallops from the Vancouver Island University breeding population, and 37 scallops obtained from a commercial farm off Vancouver Island, British Columbia. The wild scallops are largely comprised of equally unrelated individuals, whereas cultured scallops are comprised of multiple families of related individuals. The polymorphism rate estimated in wild scallops was 1.7%, whereas in the cultured strains it ranged between 1.35% and 1.07%. Interestingly, heterozygosity rates were highest in the cultured populations, which is likely due to shellfish hatchery practices of crossing divergent strains to gain benefits of heterosis and to avoid inbreeding. Evidence of founder effects and drift were observed in the cultured strains, including high genetic differentiation between cultured populations and between cultured populations and the wild population. Cultured populations had effective population sizes ranging from 9-26 individuals whereas the wild population was estimated at 25-50K individuals. Further, a depletion of low frequency variants was observed in the cultured populations. These results indicate significant genetic diversity losses in cultured scallops in Canadian breeding programs. Article SummaryYesso scallop was introduced to breeding programs in Canada around 40 years ago and has become a valuable aquaculture species in the country with little information regarding its genetic diversity. This work genotypes over 20K genetic variants in wild Yesso scallops from Japan and compares to a major broodstock collection in British Columbia, Canada, as well as a commercial farm in the same region. Reduced polymorphism but elevated heterozygosity indicates value of using genetic information to guide breeding programs.

genomics↗

bioRxiv2020

Enterohepatic transcription factor CREB3L3 protects atherosclerosis via SREBP competitive inhibition

CREB3L3 is a membrane-bound transcription factor to maintain lipid metabolism in the liver and small intestine. CREB3L3 ablation in Ldlr-/- mice exacerbated hyperlipidemia with remnant ApoB-containing lipoprotein accumulation, developing enhanced aortic atheroma formation, whose extent was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly upregulates anti-atherogenic FGF21 and ApoA4, whereas antagonizes hepatic SREBP-mediated lipogenic and cholesterogenic genes and regulates LXR-regulated genes involved in intestinal transport of cholesterol. CREB3L3 deficiency accumulates nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs on endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 competitively antagonizes SREBPs for ER-Golgi transport, resulting in ER retention and proteolytic activation inhibition at Golgi, and vice versa. Collectively, due to this new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions, CREB3L3 has multi-potent protective effects against atherosclerosis.

physiology↗