Mycobacterium tuberculosis impairs protective cytokine production via transcription factor MafB manipulation.

Although an increased expression of the transcription factor v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) has been reported in patients with active tuberculosis (TB), its potential role in Mycobacterium tuberculosis infection remains unknown. Herein, we report that MafB in macrophages is a regulator of the pro-inflammatory cytokines, TNF-α and IL-12p40, which are crucial for host defense against M. tuberculosis infection.

Isolation and characterization of novel bacteriophages targeting Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is a bacterium often resistant to antibiotics and is a significant cause of nosocomial infections, particularly in immunocompromised patients. Phage therapy has shown promise as a potential treatment for such difficult-to-treat bacterial infections, but research on phages targeting this bacterium is very limited. In this study, we isolated 34 phages using four clinical strains of S.

Synergistic activation of bat SARS-like coronaviruses spike protein by elastase and TMPRSS2.

Although numerous sarbecoviruses have been identified in bats, but most lack the ability to infect human cells. Some barriers limit coronavirus zoonosis, including susceptibility to host proteases. Here, we investigated whether exogenous protease treatment can circumvent host restrictions in two severe acute respiratory syndrome (SARS)-related bat coronaviruses.

Optimizing the breadth of SARS-CoV-2-neutralizing antibodies in vivo and in silico.

Since the emergence of SARS-CoV-2, the ongoing arms race between mutating viruses and human antibodies has revealed several novel strategies by which antibodies adapt to viral escape. While SARS-CoV-2 viruses exhibit high variability in epitopes targeted by neutralizing antibodies, certain epitopes remain conserved owing to their essential roles on viral fitness. Antibodies can acquire broadly neutralizing activity by targeting these vulnerable sites through affinity-based somatic evolution of immunoglobulin genes.

Bivalent single-domain antibodies show potent mpox virus neutralization through M1R antigen.

Despite the recent mpox outbreak raising global concerns, no fully validated antiviral treatment exists, highlighting the urgent need for effective therapeutics. Here, by taking advantage of the preparation technology for single-domain (VHH) antibodies, we generated VHHs targeting the six major mpox virus (MPXV) surface antigens. Although neutralization activity of these monoclonal VHH monomers was negligible, bivalent VHHs against MPXV-M1R (bi-M1A8 and bi-M1C2) improved the antigen binding affinity by up to over 400-fold compared with the monomer VHH and thus produced neutralizing activity against MPXV.

A feasibility study for personalized phage therapy against drug-resistant bacteria in Japan.

Introduction: Personalized phage therapy is used in Europe and the United States to treat intractable infections caused by drug-resistant bacteria. This pilot study aimed to acquire feasibility data for clinical trials of individualized phage therapy in Japan.

Methods: An observational study was conducted from August 2023 to September 2024 in adults with drug-resistant bacterial infections and treatment failure or recurrence/relapse following antimicrobial therapy.

Antibody durability is influenced by interleukin-2 production by undifferentiated memory T helper cells and extensive B cell clonal expansion.

SARS-CoV-2-neutralizing antibody titers serve as immune correlates of protection against COVID-19; however, the durability varies among vaccinees. Here, we demonstrate that the durability of vaccine-boosted antibody responses is closely correlated with the pre-booster capacity of spike-reactive CD4 T cells to produce interleukin (IL)-2 and T helper type 2 (Th2) cytokines. IL-2 production by CD4 T cells was also associated with extensive B cell clonal expansion, which preceded the durable antibody responses.

Development of a nonreplicative phage-based DNA delivery system and its application to antimicrobial therapies.

Phage therapy has emerged as a promising alternative to conventional antimicrobial therapy for antimicrobial-resistant bacterial infections, but concerns about uncontrolled phage proliferation have limited its use. To address this issue, we established a nonproliferative phage-based DNA delivery system, called bacteria-targeting capsid particle (B-CAP), for the development of antimicrobial agents which effectively prevented phage spread while maintaining bactericidal activity. B-CAP is principally a T7 phage capsids packaged with a partial T7 phage genome, giving it the allowance to accommodate large foreign DNA up to 18 kb in length.

Prolonged effects of adenoviral vector priming on T-cell cytokine production in heterologous adenoviral vector/mRNA COVID-19 vaccination regimens.

mRNA and adenoviral vector vaccine platforms were used for the primary series of COVID-19 vaccines in many countries. However, the distinct immunogenic properties on these platforms remain less understood. We traced neutralizing antibodies, memory B cells, and T cells longitudinally in cohorts that received either mRNA (BNT162b2 or mRNA-1273) or adenoviral vector (ChAdOx1) vaccines with homologous or heterologous regimens (total 9 groups, n = 26-28 for each group) at 4 weeks interval.

A protective and broadly binding antibody class engages the influenza virus hemagglutinin head at its stem interface.

Unlabelled: Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here, we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein.

Establishment of a novel adjuvant screening system for the development of intranasal vaccine adjuvants.

Vaccine adjuvants play a pivotal role in enhancing the immunogenicity of vaccines. Some vaccine modalities, such as subunit vaccines and split vaccines, are inherently poorly immunogenic and benefit greatly from combination with adjuvants. Notable examples, such as the herpes zoster glycoprotein E subunit vaccine and the Novavax COVID-19 (NVX-CoV2373) vaccine, underscore the importance of adjuvants in vaccination.

Immunological analysis of LC16m8 vaccine: preclinical and early clinical insights into mpox.

Background: The global mpox outbreak (2022-2024) highlights the need for effective and safe vaccines, particularly for vulnerable populations. The LC16m8 vaccine, an attenuated vaccinia virus strain for smallpox, shows promise in inducing immunity against the monkeypox virus (MPXV).

Methods: We conducted a comprehensive immunological evaluation of LC16m8 in mice, non-human primates, and humans.

The constitutive presence of commensal bacteria contributes to the abundance of cecal IgG2b B cells and the supply of serum IgG2b reactive to commensal bacteria in adult mice.

Immunoglobulin (Ig) G isotypes in the sera of healthy mice and humans react to commensal bacteria. We previously reported that BALB/c mice with normal gut microbiota possessed abundant B cells that produced IgG2b reactive to commensal bacteria in cecal patches (CePs), indicating a potential source of a systemic pool of commensal bacteria-reactive IgG2b. Mice housed under germ-free conditions demonstrate the importance of the gut microbiota in driving cecal IgG2b responses.

Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants.

Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood.

Cross-Reactive Fc-Mediated Antibody Responses to Influenza HA Stem Region in Human Sera Following Seasonal Vaccination.

Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of universal vaccine research due to its cross-protective potential. Additionally, Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are recognized as important protective immune mechanisms.

Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination.

Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated the neutralizing activity of recalled antibodies, primarily targeting an immunodominant site III epitope with hydrophilic and rugged structures.

Phage engineering to overcome bacterial Tmn immunity in Dhillonvirus.

Bacteria possess numerous defense systems against phage infections, which limit phage infectivity and pose challenges for phage therapy. This study aimed to engineer phages capable of evading these defense systems, using the Tmn defense system as a model. We identified an anti-Tmn protein in the ΦSMS22 phage from the Dhillonvirus genus that inhibits Tmn function in Escherichia coli.

Calboxyvinyl polymer adjuvant enhances respiratory iga responses through mucosal and systemic administration.

Adjuvants play a crucial role in enhancing vaccine efficacy. Although several adjuvants have been approved, there remains a demand for safer and more effective adjuvants for nasal vaccines. Here, we identified calboxyvinyl polymer (CVP) as a superior mucosal vaccine adjuvant from pharmaceutical base materials using our screening systems; single nasal vaccination of the CVP-combined influenza split vaccine-induced antigen-specific IgA and IgG antibodies and provided protection against lethal influenza virus infection.

Atypical memory B cells from natural malaria infection produced broadly neutralizing antibodies against Plasmodium vivax variants.

Expansion of atypical memory B cells (aMBCs) was demonstrated in malaria-exposed individuals. To date, the generation of P. vivax-specific aMBCs and their function in protective humoral immune responses is unknown.

An outbreak of influenza A(H1N1)pdm09 antigenic variants exhibiting cross-resistance to oseltamivir and peramivir in an elementary school in Japan, September 2024.

An outbreak of influenza A(H1N1)pdm09 viruses exhibiting cross-resistance to oseltamivir and peramivir occurred in Yokohama, Japan, in September 2024. Among 24 students in a class, 11 were diagnosed with influenza or influenza-like illness, and viruses harbouring the NA H275Y and HA Q210H substitutions were isolated from four. Deep sequencing analysis confirmed the clonal spread of these mutants.

Analysis of antigen specificity of Treg clonotypes expanded upon SARS-CoV-2 infection.

The pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses.

Evasion of antiviral bacterial immunity by phage tRNAs.

Retrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action of most retron effectors, and how phages evade retrons, are not well understood. Here, we show that some phages can evade retrons and other defense systems by producing specific tRNAs.

Repeated Omicron exposures redirect SARS-CoV-2-specific memory B cell evolution toward the latest variants.

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.