ETIDIOH - NEW

  Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters . Despite case fatality rates (CFRs) of over 30% and considerable pandemic potential , a safe and efficacious vaccine has not been developed. Here we report the design, characterization, and preclinical evaluation of MERS-CoV antigens . Our lead candidate comprises a stabilized spike displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool . This vaccine elicits robust MERS-CoV pseudovirus and authentic virus neutralizing antibody titers in BALB/c mice. Immunization of male non-human primates (NHPs) with one dose of Alhydrogel-adjuvanted vaccine elicited a > 103 geometric mean titer of pseudovirus neutralizing antibodies that was boosted with a second dose. Sera from these NHPs exhibited cross-reactivity against spike-pseudotyped lentiviruses from MERS-C...

  Abstract Introduction Seasonal influenza causes significant global morbidity, mortality, and economic burden . Ongoing viral evolution can lead to vaccine mismatch and the emergence of antiviral resistance , highlighting the importance of genomic surveillance. The 2024–2025 influenza season was characterized by high incidence and increased hospitalizations. Methods We analyzed influenza A virus (IAV) genomes and clinical characteristics from the 2024–2025 season . Whole-genome sequencing was performed on 648 influenza A–positive clinical specimens collected between October 2024 and April 2025. Results Hemagglutinin (HA) sequences were recovered from 74.23% (481/648) of samples and used for subtyping and phylogenetic analysis. A(H1N1)pdm09 and A(H3N2) viruses co-circulated , representing 55.5% and 44.5% of cases, respectively. Among A(H1N1)pdm09 viruses, the HA1 substitution T120A , located near the Sa antigenic site , increased more than twofold compared with the prior season. Ci...

  Abstract Highly pathogenic avian influenza H5N1 virus has spread to over 1,080 dairy farms across 18 states in the United States, resulting in 41 human infections and posing serious risks to both animal and public health . To address these risks, a hemagglutinin-based mRNA–lipid nanoparticle vaccine was developed , and its safety, immunogenicity, and protective efficacy in high-yielding lactating dairy cows were evaluated. The vaccine was well tolerated, had no adverse effects on health or milk production , and induced strong antibody responses . Two weeks after the second immunization, all the immunized cattle were fully protected against a high-dose H5N1 virus challenge . Notably, two-thirds of the cattle were still completely protected even at the 19th week after the first vaccination , when their serum antibody levels were very low. These data demonstrate that the mRNA vaccine confers robust, lasting protection against H5N1 virus in lactating dairy cows, providing a foundatio...

  {Summary} Recent headlines about influenza have reported a “super flu” causing a “record-breaking season” that is “overwhelming hospitals.” Although less dramatic, data from the Centers for Disease Control and Prevention (CDC) reveal substantial influenza activity : the agency estimated that there were more than 20 million cases of influenza illness, 270,000 influenza-related hospitalizations , and 11,000 deaths from influenza in the United States through January 24, 2026. These numbers aren’t extraordinary as compared with those from previous seasons, but some indicators of influenza activity and severity have been remarkable. (...) Source:  Link:  https://www.nejm.org/doi/full/10.1056/NEJMp2600395?query=TOC ____

  Highlights •  IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses •  IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters •  IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery •  ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity Summary The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic . To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents . Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell respon...

  Abstract We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity . Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift . Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity . These findings provide timely insight for interpreting recent influenza epidemiology and informing vaccine strain selection. Competing Interest Statement The following authors declare no conflict of interests: KD, RI, LM, SR, HC, GGA, MSA, VS, ZW, SKW, JZ, BJW, DLR, JH, OML, JG, CJRI. PRM receives funding for research work for MSD. EH has received an honorarium for advisory board work for Seqirus. ET has received funding from Novavax and Astra Zeneca. Funding Statement This work was funded by the Medical Research Council (MRC) to the MRC-Universi...

  Abstract Influenza A viruses continually pose pandemic threats, underscoring the need for timely development of Candidate Vaccine Viruses (CVVs) that meet regulatory expectations for vaccine manufacturing. This protocol describes the procedures used at CDC to generate recombinant CVVs through reverse genetics in accordance with World Health Organization guidelines and CDC’s internal Quality System Requirements (QSR)1,2,3. The QSR incorporates relevant principles from the FDA’s Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) regulations, providing a structured framework that ensures documentation integrity, material traceability, and quality oversight during all stages of CVV development. The protocol provides detailed steps for plasmid preparation , virus rescue in Vero cells , and amplification in embryonated chicken eggs , and outlines characterization assays used to confirm the suitability and safety attributes of each CVV. This standardized, quality-drive...

  ABSTRACT Vaccinia virus (VACV) confers cross-protective immunity against monkeypox virus (MPXV), the causative agent of mpox, and has therefore been extensively exploited as a preventive vaccine . VACV Tiantan strain (VTT) is a second-generation smallpox vaccine used in China in the last century, and there are consistent efforts to minimize its virulence and ensure its best safety for potential clinical applications. In this study, an attenuated VACV rVTT△C12K2△A45 was constructed by deletion of gene segments related to virulence genes , host range genes, immune regulatory genes, and other functional genes from the VTT genome by genetic engineering. Attenuation characteristics of rVTT△C12K2△A45 were confirmed by smaller plaque size, lower replication capacity in various mammalian cell lines along with tests for neurotoxicity in mice , and lesion formation on rabbit skin . Immunization in BALB/c mice with rVTT△C12K2△A45 induced both anti-MPXV and anti-VACV neutralizing antibodies ...

  Abstract The continuous evolution and global spread of highly pathogenic avian influenza (HPAI) H5N1 viruses , particularly clade 2.3.4.4b, pose major challenges for pandemic preparedness . This study evaluates a low-dose inactivated split-virus vaccine derived from H5N1 clade 2.3.4.4b, formulated with an Alum/CpG adjuvant , in a preclinical female mouse model . The vaccine induces strong humoral and cellular immunity , generating high titers of cross-reactive antibodies against diverse H5 hemagglutinin (HA) and across different N1 neuraminidase (NA) glycoproteins. The Alum/CpG adjuvant supports substantial antigen dose sparing and promotes a balanced Th1/Th2 profile. Functional assays show potent virus neutralization , neuraminidase inhibition , and antibody-dependent cellular cytotoxicity , alongside robust antigen-specific CD4+ and CD8+ T cell responses, efficient control of lung viral replication, and reduced lung inflammation . Vaccinated mice are fully protected from lethal...

  Abstract Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate . Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines , a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied . Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms . The mRNA EBOV-GP vaccine , formulated in lipid nanoparticles , elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinc...

  Abstract The association between vaccine efficacy (VE) and force of infection (FoI) remains incompletely understood . Previous analyses have been primarily based on trial-level summary data—not accounting for the effect of time and constrained by the number of trials. Here, we leverage individual-level data from three phase 3 randomized, placebo-controlled COVID-19 vaccine trials —the COVE trial (Moderna, CoVPN3001), the AZD1222 trial (AstraZeneca, CoVPN3002), and the ENSEMBLE trial (Janssen/Johnson & Johnson, CoVPN3003)—and contemporaneous geographic-location-specific SARS-CoV-2 surveillance data from the start of the pandemic through November 14, 2021 (including the blinded follow-up periods of the trials) to conduct five cohort- and vaccine-specific analyses: COVE (U.S.), AZD1222 overall (U.S. + non-U.S.), AZD1222 U.S., ENSEMBLE overall (U.S. + non-U.S.), and ENSEMBLE U.S. In AZD1222 U.S., higher VE was associated with higher FoI (p = 0.01). In ENSEMBLE overall, lower VE w...

  Abstract Annual influenza vaccination is the cornerstone for seasonal protection, yet antibody responses are highly variable across individuals and over time. To systematically assess the determinants of this heterogeneity, we compiled 20,449 hemagglutination inhibition and neutralization titers from 4,540 participants enrolled in 14 new vaccine studies we conducted and 50 prior studies that collectively span 2010-2023. Seasonal effects dominated , with pre- and post-vaccination titers declining steadily from 2017 onwards, outweighing the influence of age, sex, or repeated vaccination. Titers to B Yamagata remained steady throughout all years examined, suggesting unique durability and offering a reason for lineage extinction . Vaccine timing emerged as a strong and previously underappreciated determinant of immunity, with individuals vaccinated later in the season exhibiting larger post-vaccination titers . Not being vaccinated or receiving the live-attenuated FluMist vaccine in ...

  Abstract Influenza causes substantial morbidity and mortality worldwide. This randomized, open-label, phase 1 trial (ClinicalTrials.gov, NCT05397223, date of registration: May 31, 2022) compared the immunogenicity of an mRNA-based quadrivalent influenza hemagglutinin (HA) vaccine (mRNA-1010) with a licensed comparator (FLUAD) in adults aged 18-75 years . We evaluated humoral and cellular immune responses using hemagglutination inhibition assays , flow cytometry-based memory B cell (MBC) profiling, and intracellular cytokine staining for T-cell characterization. Both vaccines elicited durable hemagglutination inhibition titers and increased HA-specific MBC responses across four vaccine strains. Compared with FLUAD, mRNA-1010 induced higher frequencies of classical and activated MBCs specific to the H3 HA included in the vaccine, while inducing similar MBC responses to the other strains. mRNA-1010 and FLUAD generated strong HA-specific CD4+ T-cell responses; a trend toward higher C...

  ABSTRACT Oropouche virus (OROV) is reemerging in the Americas, along with a growing threat to global public health . Recent outbreaks have witnessed the first reported fatalities , vertical transmissions , and intercontinental importations of OROV, underscoring its expanding risk . Despite this, no vaccines or specific therapeutics are available, and fundamental research on OROV vaccinology and antigenicity remains limited. Here, we show that co-expression of the M polyprotein and nucleocapsid protein (NP) drives the assembly of OROV virus-like particles (VLPs) with high immunogenicity . Using the prototype strain OROV/sloth/Brazil/PA-UG-BeAn19991/1960, we developed an mRNA vaccine, M/N-vac, encoding these VLPs . Immunization with M/N-vac in mice elicited robust OROV-specific IgG and pseudovirus-neutralizing antibodies that cross-reacted with a contemporary circulating strain, hOROV/Brazil/AM-UKY-AM0088/2024. The vaccine also induced a durable, antigen-specific Th1-biased cellula...

  {Excerpt} 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 2025–26 season vaccines , following recommendations issued by 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 variants, as well as LP.8.1, are derived from JN.1 . Moreover, BA.3.2, a BA.3 descendant bearing multiple mutations in its spike gene , has potentially been spreading and exhibiting robust immune evasion . In Japan, the roll-out 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 2023,6 and the JN.1-based monovalent vaccine in 2024 in the Japanese populat...

  Abstract Seasonal and pandemic influenza viruses are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration , reducing the ability to establish local protective immune responses such as respiratory mucosal immunity . Here, we describe monovalent and bivalent replicon vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/PA-1/2013 H7N9. These replicon vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice , IM vaccination established systemic humoral and cellular responses but no detectable mucosal response , while IN administration induced robust systemic and mucosal immunity . The replicon-NLC vaccines protected against morbidity and m...

  Abstract The emergence and broad circulation of highly pathogenic avian influenza (HPAI) H5N1 virus in wild birds and its spillover into dairy cows with sustained transmission in this species pose a major risk to felines , which are highly susceptible and often succumb to the infection . Here, we developed a novel recombinant hemagglutinin H5-based vaccine and evaluated its safety, immunogenicity, and protective efficacy against HPAI H5N1 virus in domestic cats . Immunization of cats with H5-vaccine candidate elicited robust levels of neutralizing antibodies against H5N1 virus and protection against disease, mortality, and infection upon H5N1 virus challenge. The vaccine-elicited immunity significantly reduced virus shedding and viremia , limiting systemic spread and disease severity in immunized animals. Importantly, beyond protecting susceptible felids, vaccinating cats against the H5N1 virus could also reduce the risk of human exposure - underscoring the One Health impact of i...

  Abstract Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic . Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States . These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies . In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodi...

  ABSTRACT Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations . We analyzed 60 A(H3N2)-positive nasopharyngeal specimens collected during the 2017–2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties . Deep sequencing revealed frequent genome-wide intrahost polymorphisms , including amino acid variants within major hemagglutinin (HA) antibody-binding sites . Virus propagation imposed rapid purifying selection, markedly reducing intrahost genetic diversity . Serological analyses demonstrated that these selective events altered antigenic properties, indicating that culture adaptation can alter antigenic profiles . To assess the functional impact of HA polymorphisms, we generated mixed viral populations containing defined ratios of HA-160K, HA-160T, and HA-160I variants identified in clini...

  {Abstract} Background :  Emerging threats such as highly pathogenic influenza strains like H5N1 emphasize the need for vaccines that induce cross-reactive immunity against conserved epitopes. Existing influenza vaccines primarily elicit strain-specific responses , leaving gaps in protection against pandemic subtypes. This study aimed to evaluate T cell responses to seasonal influenza A and H5N1 and compare them to SARS-CoV-2 specific T cell responses to understand differences shaped by distinct exposure histories and vaccination strategies. Methods :  T cell responses were assessed in 41 laboratory workers who received annual seasonal influenza vaccines using ELISpot to quantify responses to peptide pools derived from influenza ( H1N1 hemagglutinin [HA], H3N2 HA, H5N1 HA, matrix protein 1 [MP1], nucleoprotein [NP]) and SARS-CoV-2 (spike [S2S], nucleocapsid [S2N]). Ten-day expansion assays were used to evaluate functional cross-reactivity between H1, H3, and H5 HA. Intra...