Assessment of a recombinant influenza virus carrying interleukin 7 gene as a platform for novel immunotherapeutic approaches.

Lineage-specific pulmonary transcriptome landscape of coronavirus infection unveils universal immunotherapy for viral pneumonia.

Over the past decades, respiratory virus infections have led to millions of cases of critical illness and deaths in humans. However, the high mutation rate of respiratory viruses greatly reduces the effectiveness of virus-target countermeasures such as vaccines and antibodies, necessitating the development of host-target immunotherapies. In a hamster model of SARS-CoV-2 infection, we observed diverse disease outcomes, delineated the variant-specific lung transcriptome landscape and demonstrated that a rational combination of pharmacological targeting of innate and adaptive immune responses is sufficient to reduce mortality and severe illness caused by beta, delta and EG.1 variants. The synergism of Poly IC-mediated activation of the innate immune response and FK506-mediated inhibition of the adaptive immune response resulted in significant suppression of both viral load and lung injury. Notably, this strategy is also available in humanized mice infected with SARS-CoV-2, H1N1 and H3N2 influenza viruses, suggesting a potent cross-virus broad-spectrum therapeutic effect.

Small Genome vs. Complex Retrovirus: Theoretical Considerations of Influenza A and HIV-1 Replication and Therapeutic Exploitation

Influenza A virus (IAV) remains a significant global health threat due to its rapid mutation rate, seasonal epidemics, and pandemic potential. Continuous viral evolution and emerging resistance to existing antivirals necessitate the evaluation of alternative or repurposed antiviral strategies. Tenofovir alafenamide (TAF), a phosphonamidite prodrug of tenofovir primarily used in antiretroviral therapy, has demonstrated intracellular stability and a favorable safety profile. In this study, we investigated the time- and concentration-dependent antiviral activity and cytotoxicity of TAF in Influenza A–infected cell culture over a 120-h period. Antiviral efficacy was quantified as percentage inhibition of viral replication, while cytotoxicity was assessed using the MTT assay to determine cell viability. TAF exhibited progressive, exposure-dependent suppression of Influenza A replication, with inhibition exceeding 80% at higher concentrations after prolonged incubation. Importantly, host cell viability remained ≥70% under corresponding conditions, and the CC₅₀ was not reached within the tested concentration range. The estimated EC₅₀ values indicated significant antiviral activity with a favourable selectivity window. These findings suggest that TAF exerts time-dependent inhibitory effects on Influenza A virus while preserving cellular viability, supporting further investigation of nucleotide-analogue–based strategies for RNA virus replication control.

H3N2 Influenza: Clinical Insights, Antiviral Resistance, and Next-Generation Strategies for Global Control

H3N2 influenza remains a persistent health concern worldwide, as it undergoes rapid antigenic drift, leading to vaccine mismatch and the development of antiviral resistance. It has a clinical manifestation with mild respiratory illness to severe complications, with a disproportionate impact on children, the elderly, and immunocompromised populations, with epidemiological evidence confirming its high socioeconomic burden. The presence of other respiratory pathogens further complicates the diagnosis and treatment of the problem and increases the need for multiplex diagnostics and integrated surveillance platforms. Although seasonal vaccines have improved, they have been reported to be less effective against H3N2 due to antigenic variation and egg-adapted mutations, leading to the consideration of next-generation approaches, including universal and mRNA-based vaccines as well as nanotechnology-based vaccines, with the capacity to induce broad and long-lasting protection. Simultaneously, the emergence of antiviral resistance in selected H3N2 strains indicates the necessity of new antivirals, combination therapy, and host-directed therapy to improve clinical outcomes. Enhancing real-time genomic monitoring, fast diagnostic capacity, and worldwide data exchange is crucial to monitor virus evolution, inform vaccine strain selection, and support emerging artificial intelligence-assisted and precision public health approaches. H3N2 influenza needs a multi-pronged strategy to be effectively controlled through the integration of innovative vaccine technologies, innovative therapeutic strategies, and robust international collaboration to guarantee fair access and scalable interventions. Finally, it will be important to translate these scientific developments into clinical and population health practice to decrease the global burden of H3N2 influenza and enhance preparedness for future seasonal epidemics and pandemic threats.

Inhibitors of the Influenza Virus Polymerase Basic 2 (PB2): Recent Advances and Future Perspectives.

Influenza, an acute respiratory infectious disease caused by influenza viruses, poses a serious public health threat with high infectivity and virulence. Existing antivirals suffer from numerous limitations, such as the frequent emergence of drug resistance and inconvenient administration, highlighting the urgent need for the development of next-generation anti-influenza agents. As a core component of the RNA-dependent RNA polymerase (RdRp) complex, the PB2 subunit mediates cap binding in the cap-snatching process, a prerequisite for viral mRNA transcription. Owing to its indispensable biological roles, high sequence conservation, and distinct structural differences from host proteins, PB2 serves as an attractive therapeutic target for antiviral drug development. Recently, the approval of onradivir, the first-in-class PB2 inhibitor, has not only validated the scientific rationale and feasibility of drug discovery targeting the PB2 subunit but also underscored the considerable clinical potential of this novel class of agents. In this review, we systematically summarize the research advances in PB2 inhibitors and discuss the challenges and prospects for their broader clinical application, with the aim of providing new insights into the development of novel anti-influenza drugs.

Development of attenuated and inactivated Dengue strains using advanced gene editing tools

TLR2/TLR7 Conjugated Adjuvant Enhances Anti-Nucleoprotein Immunity and Provides Protection Against Lethal H1N1 Influenza Infection 2253752

Influenza A virus (IAV) poses a significant public health threat due to its high mutation rate. Antigenic drift (slight changes in the outer coat proteins) leads to seasonal epidemics, while antigenic shift (new hemagglutinin (HA) or neuraminidase (NA) antigens) can produce novel strains with pandemic potential. Limited population immunity to these new strains increases the risk of severe illness and mortality, underscoring the urgent need for a universal vaccine. To develop a universal influenza A virus (IAV) vaccine that induces robust B and T cell memory responses we take a two-layered approach. First, we utilize toll-like receptor (TLR) agonists as vaccine adjuvants and second, we add a conserved internal protein (nucleoprotein (NP)) to increase the breadth of the immune response and activate T cell responses to provide a second armament of protection. We show that a conjugated, dual TLR2/7 agonist CL413 and NP antigen can enhance both antibody and T cell responses after intramuscular (i.m.) injection and provide enhanced heterosubtypic immunity to lethal IAV infection compared to either agonist alone. In determining the utility of this approach across mouse strains we found that BALB/c mice generated a hyperinflammatory response to the initial i.m. vaccination with CL413 and antigen, with the TLR2 agonist being responsible for the higher side effects. In contrast, the i.m. injection of CL413 (or TLR agonist) in C57BL/6 strain showed no adverse outcomes. Interestingly, vaccination of BALB/c mice via the intranasal (i.n.) route did not induce visible side effects, yet provided complete protection against challenge. Together, these data indicate that conjugated adjuvants with conserved IAV proteins provide superior heterosubtypic protection compared to antigen alone, or antigen with singular agonists. Investigating the protective mechanisms of this combination strategy, brings us closer to developing a universal vaccine against both seasonal and pandemic IAV strains. Biomedical Research Scholars Program, Trudeau Institute Vaccines and Immunotherapy (VAC)