ETIDIOH - NEW

Abstract H9N2 avian influenza virus (AIV) is a globally prevalent pathogen that causes economic losses in poultry and poses zoonotic threats . Due to antigenic drift and shift, traditional inactivated vaccines often show reduced efficacy . This study presents a novel subunit vaccine based on a conserved HA6 scaffold derived from the hemagglutinin stem domain and coupled with a fusion peptide epitope (fPE) via Snoopligase-mediated ligation. The HA6 protein was validated by its binding to the broad-spectrum antibody CR6261, and the fPE-HA6 fusion construct incorporated T- and B-cell epitopes. Immunization trials in a chicken demonstrated that fPE-HA6 induced stronger humoral and cellular immune responses than individual immunogens. Upon challenge with H9N2 strains YZ4 and SN, the fusion vaccine significantly reduced viral shedding, demonstrating broad-spectrum protection. These findings highlight the potential of HA6 as a modular scaffold for influenza vaccines and the utility of Snoopli...

Abstract H5N1, a highly pathogenic avian influenza virus, presents pandemic risks due to its ability to adapt and spread among mammalian species . Vaccination may control its spread, but the effectiveness of existing H5N1 vaccines against circulating strains, especially clade 2.3.4.4b, remains uncertain . In this study, we assess neutralizing antibody responses to global circulating H5N1 strains, using sera from individuals vaccinated with an inactivated H5N1 vaccine (NCT00535665). Neutralization is measured against 17 pseudoviruses, representing circulating and vaccine H5 strains. Our results indicate that broad protective effects are observed only when high antibody titers are achieved by vaccination. Correlation analysis estimates that a pseudovirus-based neutralization titer of at least 1:980 is required to achieve a cross-protection rate above 60%. The findings suggest that the current H5N1 vaccine can elicit cross-neutralization of circulating H5N1 strains , if high antibody tite...

ABSTRACT The threat to global health security posed by Middle East respiratory syndrome coronavirus (MERS-CoV) and emerging MERS-like coronaviruses highlights the need to develop safe and efficient vaccines. Viral vector vaccines have been shown to be effective and are widely used to prevent various viral diseases because they mimic natural infection and induce a more comprehensive immune response. Herein, we developed a novel bat influenza A virus-based vaccine vector by replacing the open reading frame of either bat influenza hemagglutinin or neuraminidase with that of the hemagglutinin-esterase-fusion gene from influenza D virus , which can infect multiple species, including humans and camels . We then generated a temperature-sensitive, cold-adapted, and attenuated MERS vaccine candidate expressing the clade A MERS-CoV spike S1, referred to as Len_S1, using the developed bat influenza vector and demonstrated its safety and immunogenicity. A single-dose intranasal immunization with L...

Abstract Background/Objectives : H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern.  Methods :  The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity.  Results :  Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale ...

Abstract Since its emergence in 1996, the H5 avian influenza virus (AIV) A/Goose/Guangdong/1/1996 (Gs/GD) haemagglutinin (HA) has evolved into over 30 genetically and antigenically distinct clades , including the widespread clade 2.3.4.4b. Vaccination is widely used in endemic regions to reduce poultry losses and zoonotic risk . However, the evolving antigenic diversity and global co-circulation of multiple clades challenges protective efficacy of poultry vaccines with poor antigenic matching to field strains, resulting in immune escape and vaccine failure. This study aimed to improve vaccine seed selection by identifying HA epitopes contributing to inter-clade antigenic differences. Recombinant clade-representative viruses were generated using HA genes from circulating H5 AIVs via reverse genetics with A/Puerto Rico/8/1934 (PR8) internal and neuraminidase genes. Antigenic relationships were assessed using haemagglutination inhibition (HI) assays with homologous and heterologous chicke...

Abstract We conducted genomic surveillance of seasonal influenza during the 2022-2023 northern hemisphere flu season on a large university setting in Southwest Arizona USA to understand the diversity, evolution, and spread within a local environment and how it relates to national data. Through high-throughput sequencing and bioinformatics, we identified 100 positive samples (19%) from 516 clinical swabs collected at the student health clinic. We observed a dominance of subtype A(H3N2) which was consistent nationally for the 2022-2023 season. However, we found stark differences when examining subtype-specific H3 clades , which included an early dominance of clade 2a.3a.1 variants contrasting from country-level data in which 2b variants were most abundant. These variants might have contributed to the early seasonal peak on campus which lagged national trends by one month. We used phylodynamics to understand the timing, source, and impact of clade-specific introductions on campus and obse...

Abstract Highly pathogenic avian influenza causes substantial poultry losses and zoonotic concerns globally . Duck vaccination against highly pathogenic avian influenza began in France in October 2023. Our assessment predicted that 314–756 outbreaks were averted in 2023–2024, representing a 96%–99% reduction in epizootic size, likely attributable to vaccination. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/7/24-1445_article ____

Abstract Seasonal influenza viruses continue to pose a significant threat, causing substantial morbidity and mortality in the US and worldwide despite the availability of vaccines and antivirals. These challenges may be addressed by improving vaccine immunogenicity through the inclusion of adjuvants that enhance immune responses against key antigens including influenza hemagglutinin (HA). BECC (Bacterial Enzymatic Combinatorial Chemistry) adjuvants are novel Toll-like Receptor 4 (TLR4) ligands created by modifying enzymes from lipid A synthesis pathways in Gram-negative bacteria. This study compares the ability of the biological and synthetic versions of these adjuvants to enhance the efficacy of recombinant HA (rHA) antigens in mouse influenza virus challenge . Mice immunized with rHA adjuvanted with BECCs stimulate the humoral and cell-mediated arms of the immune system without exhibiting cytotoxicity/pyrogenicity. A robust HA-specific immunoglobulin subtype, especially IgG2a, respon...

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...

Highlights •  Different immune responses in mice vaccinated with influenza A(H5N1) than with other subtypes. •  Highly pathogenic avian influenza A(H5N1)-vaccinated mice had altered germinal center responses. •  A(H5N1)-vaccinated mice had fewer dLN germinal centers and more extrafollicular B cells. •  A(H5N1)-vaccinated mice had more dLN follicular helper and regulatory T cells. •  Our study represents a timely assessment of A(H5N1) risk to human health. Abstract Highly pathogenic avian influenza (HPAI) H5N1 virus vaccines typically yield lower neutralizing antibody titers in animals than influenza A virus (IAV) vaccines derived from other viral subtypes. To understand these differences, we compared the cellular immune responses in the draining lymph nodes (dLNs) of mice vaccinated with an inactivated whole H5N1 vaccine to those in mice vaccinated with seasonal H1N1pdm09, H7N9, or H9N2 IAV vaccines . H5N1-vaccinated mice exhibited reduced serum neutralizing ant...

Summary Background The JYNNEOS modified vaccinia virus Ankara vaccine is effective in preventing clade IIb mpox disease . However, vaccine effects on mpox severity are poorly understood. We aimed to assess associations between reported clinical characteristics and vaccination status among individuals with laboratory-confirmed mpox. Methods We conducted a case–control study using data collected from public health surveillance interviews of people with mpox in California . Eligible participants for primary analyses were men who were cisgender and participated in telephone interviews with complete responses recorded about anatomical sites where they had lesions. We estimated JYNNEOS vaccine effectiveness against progression to disease involving disseminated lesions via the adjusted odds ratio of vaccination, comparing participants who reported lesions disseminated across multiple anatomical regions (cases) with participants who reported lesions contained to a single anatomical region (con...

Agreement’s adoption follows three years of intensive negotiation launched due to gaps and inequities identified in national and global COVID-19 response. Agreement boosts global collaboration to ensure stronger , more equitable response to future pandemics. Next steps include negotiations on Pathogen Access and Benefits Sharing system. Member States of the World Health Organization (WHO) today formally adopted by consensus the world's first Pandemic Agreement. The landmark decision by the 78th World Health Assembly culminates more than three years of intensive negotiations launched by governments in response to the devastating impacts of the COVID-19 pandemic, and driven by the goal of making the world safer from – and more equitable in response to – future pandemics. “The world is safer today thanks to the leadership , collaboration and commitment of our Member States to adopt the historic WHO Pandemic Agreement,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.  “The Ag...

Abstract Highly pathogenic avian influenza (HPAI) H5N1 has been a global concern since its emergence in 1997, causing widespread outbreaks in birds and sporadic human infections . The clade 2.3.4.4b H5N1 virus has rapidly expanded across continents, infecting numerous mammalian species . In 2024, it was detected in dairy cattle for the first time in the U.S., along with human cases following exposure . In Canada , the first human case of this avian influenza was reported in a critically ill adolescent in late 2024. No human-to-human transmission has been documented, but concerns persist regarding mutations associated with enhanced virulence and human adaptation . Although seasonal influenza vaccines are not directed against H5N1, studies suggest that pre-existing immunity from prior infections or vaccinations may provide partial protection against severe H5N1 infections through cross-reactive immune response . Given the ongoing circulation of avian influenza and the rise in human infec...

  Key points -- Vaccination remains an important public health countermeasure against COVID-19 . As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE). -- SARS-CoV-2 continues to undergo sustained evolution since its emergence in humans, with important genetic and antigenic changes in the spike protein. -- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants. -- The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advises manufacturers that monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens ; monovalent LP.8.1 is a suitable alternative vaccine antigen . -- In accordance with WHO SAGE policy, vaccination should not be delayed in anticipation of access to vacci...

Abstract We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article ____

ABSTRACT The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns . Using a previously established pseudovirus-based neutralization assay , we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations . These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation , present in 47.8% of sequences, markedly contributed to antibody escape . Our findings highl...

Abstract The GreVac vaccine technology was created as a fast and flexible plug-and-play vaccine platform based on a 4th generation architecture of fully deleted (fd) helper virus independent (hi) adenoviral (Ad) vectors. For the initial proof-of-principle studies , we at Greffex had engineered an avian influenza vaccine , which delivered a transgene expression cassette for an avian influenza virus H5 hemagglutinin and N1 neuraminidase genes in a capsid of the common human Ad serotype 5 (Ad5). This vaccine proved highly immunogenic and protective in mice . These studies revealed that intramuscular (i.m.) delivery proved more efficient than subcutaneous (s.c.) or intranasal (i.n.) routes. In the human population, pre-exposure to the Ad5 virus is common. To minimize interference by pre-existing anti-Ad5 immunities, we created a new GreVac-based avian influenza vaccine, in which the fd Ad genome was packaged into a capsid of the rare human Ad serotype 6 (Ad6). We now report that at very lo...

Abstract The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV . We developed a SUDV vaccine candidate based on a nanocarrier (LIONTM) complexed with an alphavirus-based replicon RNA . Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection . Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses ...

Abstract Recent influenza vaccine formulations have improved the magnitude of B-cell antibody responses in older adults ; however, older adults remain significantly at risk for severe influenza-related illness . Although antibodies are an important metric of vaccine effectiveness, they only represent one aspect of the immune response. In this study, we combined in vitro and ex vivo assays with human samples to investigate B, CD4+ T, and myeloid cell responses to influenza vaccine antigens . We found that older adults mounted equivalent antibody titers to younger adults but had fewer influenza-specific CD4+ T cells and reduced antiviral-associated T helper cell populations. Single-cell transcriptomics revealed that older adults had attenuated interferon transcriptional signatures in T helper and myeloid cell subsets . These data suggest that with aging, transcriptional programming alterations in myeloid cells contribute to reduced antiviral T cell responses, and formulating vaccines tai...