ETIDIOH - NEW

  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...

ABSTRACT Faced with the global monkeypox outbreak, current vaccine development predominantly focuses on the mRNA platform despite its limitations in stability and long-term efficacy. Here, we engineered a recombinant vesicular stomatitis virus (rVSV)-vectored cocktail vaccine encoding four conserved monkeypox virus (MPXV) antigens (A35R, A29L, M1R, and B6R; >94% clade homology), leveraging the thermostable properties of the VSV platform validated for 4°C storage in Ebola vaccines. In BALB/c mice , this multi-antigen vaccine elicited a rapid humoral response with specific IgG detectable by day 7, effectively neutralized the virus, and induced a robust Th1/Th2 balanced cytokine response . Immunization conferred 100% survival against lethal vaccinia virus WR strain challenge , with undetectable viral loads in the lungs and serum , and sustained efficacy against secondary infection at 60 days. Histopathology confirmed minimal lung damage in vaccinated mice . Crucially, upon the successi...

  Abstract Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat , and a multivalent vaccine is the primary prophylactic measure to control these viruses. To establish such a vaccine, we generated two multivalent vesicular stomatitis virus (VSV)-based vaccine candidates (V-EtM2e/H505 and V-EtM2e/H522) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization in mice induced high humoral immune responses against both the HPAI hemagglutinin (HA) protein and the ectodomain of M2 (M2e) protein . Intriguingly, vaccine-immunized mouse sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses . Furthermore, both intranasal and intramuscular immunizati...

  Abstract SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity . We investigated this in India . Adult volunteers with hybrid SARS-CoV-2 immunity were administered FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses , highlighting vaccine immunogenicity may be subject to Treg dampening . FluarixTM did not boost SARS-CoV-2 immunity . However, SARS-CoV-2 -specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity . We observed, elevated fr...

  Abstract Up-to-date estimates of COVID-19 vaccine effectiveness (VE) are needed to inform COVID-19 vaccination strategies and recommendations . This target trial emulation study aimed to estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration . The study population (90.9% male, mean age 70.7 years) included 538,631 pairs of vaccinated (i.e., received the KP.2 COVID-19 vaccine) and matched unvaccinated (i.e., did not receive the KP.2 COVID-19 vaccine) persons enrolled from August 2024 to January 2025. Over a mean follow-up of 172 days (range 97-232) extending to April 12, 2025, VE was low against laboratory-diagnosed SARS-CoV-2 infection ( 16.60%, 95% confidence interval [CI], 11.92-21.44), SARS-CoV-2-associated emergency department/urgent care (ED/UC) visit ( 21.05%, 95% CI, 14.22-27.21), SARS-CoV-2-associated hospitalization ( 19.53%, 95% CI 6.56-30.10) and much higher again...

  Abstract We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024 , focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy . HA phylogeny ...

  Abstract Nipah virus (NiV) is a zoonotic pathogen that causes severe encephalitis and respiratory disease in humans and multiple mammalian species. However, no licensed vaccines or therapeutics are currently available against NiV infection. In this study, we developed three mRNA vaccine candidates using a lipid nanoparticle (LNP) delivery platform : mRNA-F-LNP, comprising mRNA encoding the fusion protein (F); mRNA-G-LNP, containing mRNA encoding the attachment glycoprotein (G); and mRNA-GF-LNP, in which mRNAs encoding both F and G proteins were co-encapsulated at a 1:1 molar ratio. All three mRNA-LNPs induced robust and sustained immune responses in both mice and Syrian hamsters . Sera from immunized Syrian hamster showed high levels of cross-neutralizing antibodies against both NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B) strains. Notably, all three mRNA-LNPs conferred complete protection against a lethal challenge with NiV-M in Syrian hamsters. These findings demonstrate tha...

  Key points: -- The WHO Technical Advisory Group on COVID-19 Vaccine Composition ( TAG-CO-VAC ) held its twice-yearly decision-making meeting in December 2025 to review the evolution of SARS-CoV-2, the performance of currently approved COVID-19 vaccines and the implications for COVID-19 vaccine antigen composition. -- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants. -- Following this meeting, the TAG-CO-VAC advises vaccine manufacturers that monovalent LP.8.1 is the recommended vaccine antigen. -- The previously recommended JN.1 lineage (JN.1 or KP.2) antigens remain suitable alternatives and vaccination should not be delayed in anticipation of access to vaccines with the LP.8.1 composition. -- Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating SARS-CoV-2 variants could also be considered. -- Vaccination rema...

  Summary Background An investigational multistage malaria vaccine, ProC6C, based on distinct Plasmodium falciparum epitopes from the sporozoite stage (P falciparum circumsporozoite protein [PfCSP]) and the transmission stages (Pfs230 and Pfs48/45), adsorbed to aluminium hydroxide (AlOH) and adjuvanted with Matrix-M adjuvant (ProC6C-AlOH/MM), has previously shown safety and immunogenicity in phase 1 studies. We aimed to study vaccine efficacy, safety, and immunogenicity in African adults with lifelong malaria exposure. Methods This randomised controlled double-blind vaccination and controlled human malaria infection (CHMI) study was conducted in Sotuba, a peri-urban setting in Mali . Healthy adults (aged 18–50 years), who were malaria experienced and met eligibility criteria, were randomly assigned (1:1) to receive three intramuscular injections of ProC6C-AlOH/MM (100 μg ProC6C and 50 μg Matrix-M adjuvant) or Verorab rabies vaccine (control) 4 weeks apart. Randomisation was done in...

  16 December 2025  Amid an early start to the Northern Hemisphere influenza season a new variant of the virus is rapidly gaining ground - but vaccination remains the “most effective defence”, the UN health agency said on Tuesday. Influenza and other respiratory viruses are surging, Dr Wenqing Zhang, Unit Head for Global Respiratory Threats at the Department of Epidemic and Pandemic Threats Management of the World Health Organization (WHO) told reporters in Geneva, and this year is marked by “the emergence and the rapid expansion of a new AH3N2 virus subclade ”. The new variant - called J.2.4.1 or subclade K - was first noted in August in Australia and New Zealand and has since been detected in over 30 countries, she said. “Current epidemiological data do not indicate an increase in disease severity , although this genetic shift makes a notable evolution in the virus,” Dr Zhang said. Influenza viruses are constantly evolving , she explained, which is why the influenza vaccine ...