Biology subjects

Saito, F.

Publications and source records attributed to Saito, F..

4 recordsLinked to original sources

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↗

bioRxiv2024

Robust antiviral humoral immunity induced by JN.1 monovalent mRNA vaccines against a broad range of SARS-CoV-2 Omicron subvariants including JN.1, KP.3.1.1 and XEC

As of November 2024, SARS-CoV-2 Omicron JN.1 subvariants, such as KP.2 (JN.1.11.1.2), KP.3 (JN.1.11.1.3), KP.3.1.1 (JN.1.11.1.3.1.1), and XEC -- a recombinant lineage between KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3) -- have been circulating in several countries. To control the infection with SARS-CoV-2 Omicron JN.1 subvariants, JN.1 monovalent mRNA vaccines have been developed. Some previous reports showed that the JN.1 monovalent mRNA vaccine of Pfizer/BioNTech (US/Germany) increased antiviral humoral immunity against JN.1 subvariants and XEC. However, the efficacy of other available JN.1 monovalent mRNA vaccines (e.g., Daiichi-Sankyo, Japan) remains unassessed. To validate the antiviral efficacy induced by JN.1 mRNA vaccines, sera were collected from individuals vaccinated with Pfizer/BioNTech JN.1 mRNA vaccine (N=15) or Daiichi-Sankyo JN.1 mRNA vaccine (N=19) before and 3-4 weeks after vaccination. We then performed a neutralization assay using these sera and pseudoviruses. Both Pfizer/BioNTech JN.1 vaccine (2.4-to 8.0-fold, P=0.0001) and Daiichi-Sankyo JN.1 vaccine (2.3-to 13-fold, P=0.0001) boosted antiviral humoral immunity against all variants tested with statistical significance. While the Pfizer/BioNTech mRNA vaccine encodes the full-length JN.1 spike (S), the Daiichi-Sankyo mRNA vaccine encodes the receptor-binding domain of JN.1 S. Our data suggest that the receptor-binding domain of JN.1 S can effectively induce antiviral humoral immunity against JN.1 subvariants and XEC comparable to the full-length JN.1 S. However, it should be considered that the sizes of our cohorts are relatively small (<20 donors per cohort), and donor characteristics, such as age, sex, underlying disease status, and previous SARS-CoV-2 infection, may critically affect the experimental results. Future investigations with larger cohorts will address this concern. When compared to vaccination with JN.1 mRNA vaccines, our previous investigations showed that the natural infection of JN.1 and KP.3.3 elicited poorer antiviral humoral immunity against JN.1 and its subvariants. Our results suggest that the JN.1 mRNA vaccination more robustly induces antiviral humoral immunity against recent JN.1 subvariants than the natural infection of JN.1 subvariants regardless of manufacturer. Moreover, as we reported last year, the humoral immunity induced by XBB.1.5 monovalent mRNA vaccine against XBB.1.5 was weaker than that against ancestral B.1.1. However, in the case of JN.1 monovalent mRNA vaccine, here we showed that the 50% neutralization titer against XBB.1.5 is greater than that against ancestral B.1.1. These observations imply that immune imprinting has shifted from that biased toward pre-Omicron to that biased toward Omicron, depending on the time and/or number of immune stimuli (e.g., infection and/or vaccination).

microbiology↗

bioRxiv2023

Antiviral humoral immunity against SARS-CoV-2 Omicron subvariants induced by XBB.1.5 monovalent vaccine in infection-naive and XBB-infected individuals

To control infection with SARS-CoV-2 Omicron XBB subvariants, the XBB.1.5 monovalent mRNA vaccine has been available since September 2023. However, we have found that natural infection with XBB subvariants, including XBB.1.5, does not efficiently induce humoral immunity against the infecting XBB subvariants. These observations raise the possibility that the XBB.1.5 monovalent vaccine may not be able to efficiently induce humoral immunity against emerging SARS-CoV-2 variants, including a variety of XBB subvariants (XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and HK.3) as well as BA.2.86. To address this possibility, we collected two types of sera from individuals vaccinated with the XBB.1.5 vaccine; those who had not been previously infected with SARS-CoV-2 and those who had been infected with XBB subvariants prior to XBB.1.5 vaccination. We collected sera before and 3-4 weeks after vaccination, and then performed a neutralization assay using these sera and pseudoviruses.

microbiology↗

bioRxiv2022

Dystroglycan N-terminal domain enables LARGE1 to extend matriglycan on α-dystroglycan and prevents muscular dystrophy

Dystroglycan (DG) requires extensive post-translational processing to function as a receptor for extracellular matrix proteins containing laminin-G-like (LG) domains. Matriglycan is an elongated polysaccharide of alternating xylose and glucuronic acid that is uniquely synthesized on -dystroglycan (-DG) by like-acetylglucosaminyltransferase-1 (LARGE1) and binds with high affinity to matrix proteins like laminin. Defects in the post-translational processing of -DG that result in a shorter form of matriglycan reduce the size of -DG and decrease laminin binding, leading to various forms of muscular dystrophy. However, little is known regarding mechanisms that generate full-length matriglycan on -DG (~150-250 kDa). Here, we show that LARGE1 can only synthesize a short, non-elongated form of matriglycan in mouse skeletal muscle that lacks the DG N-terminus (-DGN), resulting in a ~100-125 kDa -DG. This smaller form of -DG binds laminin and maintains specific force but does not prevent muscle pathophysiology, including reduced force induced by eccentric contractions and abnormalities in neuromuscular junctions. Collectively, our study demonstrates that -DGN is required for LARGE1 to extend matriglycan to its full mature length on -DG and thus prevent muscle pathophysiology.

biochemistry↗