ETIDIOH - NEW

  Abstract Finland faced an outbreak of highly pathogenic clade 2.3.4.4b A(H5N1) avian influenza in 2023, which spread from wild birds to fur farms . Vaccinations of at-risk individuals began in June 2024 using the MF59-adjuvanted inactivated A(H5N8) vaccine (Seqirus; A/Astrakhan/3212/2020, clade 2.3.4.4b). Here, in an observational study , we assessed vaccine-induced immune responses in occupational at-risk individuals participating in the phase IV trial , including virus-specific antibody (n = 39 individuals) and T-cell (n = 18 individuals) responses. Vaccination elicited functional antibodies against the vaccine virus and two heterologous clade 2.3.4.4b strains associated with outbreaks on Finnish fur farms and dairy cattle in the United States . Among previously unvaccinated individuals, seroprotection rates against the vaccine virus were 83% (95% CI 70–97%) by microneutralization assay (titre ≥20) and 97% (90–100%) by haemagglutination inhibition assay (titre ≥40). In those pr...

  Abstract The global spread of highly pathogenic avian influenza A(H5N1) viruses poses a serious pandemic threat . While sustained human-to-human transmission has not occurred, widespread circulation in birds , increased detection in mammals , and occasional human spillovers underscore the need for safe and effective vaccines . We evaluated an H5 mRNA vaccine candidate in ferrets using recent clade 2.3.4.4b A(H5N1) human isolates. Vaccination elicited strong neutralizing antibodies , conferred robust protection against lethal challenge , and significantly reduced viral titers . In a direct contact transmission model , mRNA vaccination decreased virus shedding in inoculated ferrets and reduced onward transmission ; it also protected vaccinated contact ferrets from infection following exposure to virus-shedding, unvaccinated ferrets. Additionally, sera from vaccinated animals cross-neutralized clade 2.3.2.1e human viruses to varying degrees, depending on the strain. These findings d...

  Summary Background The first chikungunya virus (CHIKV) vaccine is now licensed in Brazil, the country that reports the most cases of CHIKV globally ; however, the optimal use of the vaccine remains unclear owing to a poor understanding of CHIKV epidemiology and population immunity . We aimed to combine the distribution of cases and deaths reported since 2014 with seroprevalence studies to inform mathematical models that estimate the underlying rates of infection by state and year, and the underlying patterns of disease and death by age and sex. Methods We quantified the annual CHIKV infection and disease burden between 2014 and 2024 in each of the 27 federative units of Brazil using a mathematical model in a Bayesian framework that integrated serological surveys (n=12) and confirmed CHIKV disease cases (n=488 234) and CHIKV deaths (n=1719) reported between January, 2014, and September, 2024. Using this base, we estimated the potential impact of a vaccine over the period 2025–29 h...

  ABSTRACT The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in antigenically distinct variants that challenge vaccine-induced immunity. The KP.2 monovalent mRNA vaccine was deployed in 2024 to address immune escape by emerging SARS-CoV-2 subvariants . We assessed neutralizing antibody responses in 56 adults with varied exposure histories following KP.2 vaccination against emerging variants including LP.8.1, LF.7.1, NB.1.8.1, XFG, and BA.3.2 . While KP.2 vaccination enhanced neutralization against homologous variants, substantial reductions in neutralizing activity were observed against emerging Omicron variants across all exposure groups. Exposure history showed some influence on neutralization breadth , with self-reported vaccination-only participants exhibiting better cross-neutralization compared to individuals with hybrid immunity . Antigenic cartography revealed substantial antigenic distances between KP.2 and emerging variants, highli...

  {Summary} SARS-CoV-2 continues to evolve, with successive variants evading immunity established by previous infection or vaccination . In mid-2024, a vaccine tailored to the JN.1 variant was authorised by the European Medicines Agency (EMA), which boosted neutralising antibody responses and provided substantial protection against severe disease and hospitalisation.1–3 Around 6 months later, in January 2025, LP.8.1 (of the JN.1 lineage) was classified as a “ variant under monitoring ” by WHO, due to its epidemiological importance and enhanced transmission fitness relative to contemporaneous strains. After emerging in late 2024, LP.8.1 rapidly overtook the XEC variant, establishing dominance throughout the Americas and Europe by early 2025 . In the USA, LP.8.1 and its sublineages represented more than 50% of all sequences in May, 2025 (appendix p 9). Although vaccines adapted to JN.1 or its derivative KP.2 generated neutralising antibodies against LP.8.1, these titres were reduced ...

  Summary Background Two large-scale trials comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) against hospitalisation outcomes have been conducted in Denmark and Spain . We aimed to analyse the pooled data from these trials to enhance generalisability and assess the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV against severe clinical outcomes in older adults. Methods FLUNITY-HD was a prespecified, individual-level pooled analysis of two methodologically harmonised pragmatic, individually randomised trials comparing HD-IIV with SD-IIV in older adults. DANFLU-2 included adults aged 65 years or older and GALFLU included community-dwelling adults aged 65–79 years. DANFLU-2 was conducted during the 2022–23, 2023–24, and 2024–25 influenza seasons in Denmark, whereas GALFLU was conducted during the 2023–24 and 2024–25 seasons in Galicia, Spain. In both trials, participants were randomly assigned (1:1) to ...

Abstract Background Influenza remains a major health burden despite the use of licensed vaccines. Nucleoside-modified messenger RNA (modRNA) influenza vaccines have shown promising immunogenicity against influenza and an acceptable safety profile in a phase 1–2 trial. Methods In this phase 3 trial, we randomly assigned healthy adults between the ages of 18 and 64 years to receive either a quadrivalent modRNA influenza vaccine (modRNA group) or a licensed inactivated quadrivalent influenza vaccine (control group) during the 2022–2023 influenza season in the United States, South Africa, and the Philippines. The primary end point was relative efficacy, defined by the reduction in the percentage of participants with laboratory-confirmed influenza associated with influenza-like illness at least 14 days after vaccination with the modRNA vaccine, as compared with the control vaccine, and analyzed for noninferiority and superiority. Immunogenicity was evaluated by means of a hemagglutination i...

  Significance Annual influenza epidemics in the United States cause hundreds of thousands of hospitalizations . Quantifying vaccine impact is vital, yet many analyses overlook vaccines’ dual benefits : directly protecting recipients and indirectly protecting their contacts . Using a mathematical model that accounts for both effects, we estimate that vaccination prevented about 70,000 hospitalizations during the 2022–2023 season , with another 19,000 potentially avoidable if coverage met the 70% national target. Despite uncertainty in vaccine effectiveness against infection, our findings suggest that vaccinating younger adults offers substantial indirect protection for older adults. Tailoring annual vaccination campaigns by age group and state could further strengthen their public health impact. Abstract During the COVID-19 pandemic early years, infection prevention measures suppressed transmission of seasonal influenza and other respiratory viruses . The early onset and moderate s...

  Summary Background First discovered in 1999 in Malaysia, Nipah virus (NiV) causes yearly outbreaks throughout south and southeast Asia with associated mortality rates of 40–75 %. Due to the structural and sequence similarities between the NiV and Hendra virus (HeV) attachment G glycoproteins , and the extensive extant evidence of the ability of a recombinant soluble glycoprotein G (HeV-sG) to provide heterologous cross-protective immunity when used as vaccine (HeV-sG-V), this study aimed to evaluate HeV-sG-V for safety, tolerability, and immunogenicity against NiV. Methods We conducted a phase 1, single-centre, randomised, observer-blind, placebo-controlled study . Eligible participants were aged 18–49 years, healthy, and not pregnant; participants were ineligible if they were immunocompromised, had received blood products within 6 months of enrolment, had potential exposure to NiV or HeV, or had known allergies to components of the vaccine. Participants were randomly assigned in...

  Abstract Influenza pandemics arise when novel influenza virus subtypes emerge in populations with little or no pre-existing immunity . The recent expansion of H5N1 virus circulation in mammals — including documented spread in cattle and sporadic human infections — coupled with the emergence of mutations associated with enhanced pandemic potential , underscores the persistent threat of novel influenza strains. Pandemic preparedness critically depends on developing effective vaccines capable of providing broad protection across diverse viral strains. While vaccination remains the most effective strategy for preventing influenza and its complications, pandemic vaccine development faces substantial challenges . These include the rapid mutation rates characteristic of influenza viruses, driven by error-prone RNA replication, broad host range, environmental selection pressures, and frequent genetic recombination. Such factors complicate predictions of which strain will trigger the next...

  Authors: Freja CM Kirsebom{1}, Catherine Thompson{2}, Tiina Talts{2}, Beatrix Kele{2}, Heather J Whitaker{3}, Nurin Abdul Aziz{1}, Christopher Rawlinson{1}, Rebecca E Green{1}, Catherine Quinot{1}, Nicholas Gardner{1}, Elizabeth Waller{1}, Alex Allen{1}, Conall H Watson{1,4}, Suzanna LR McDonald{1}, Maria Zambon{2}, Richard Pebody{4,5}, Mary Ramsay{6,7}, Katja Hoschler{2}, Anika Singanayagam{*2,4}, Jamie Lopez Bernal{*1,4}  {*} Joint last authors  {1} Immunisation and Vaccine-preventable Diseases Division, UK Health Security Agency, Colindale, London  {2} Respiratory Virus Unit (RVU), UK Health Security Agency, Colindale, London  {3} Modelling Division, UK Health Security Agency, Colindale, London  {4} NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, United Kingdom  {5} Epidemic and Emerging Infections Directorate, UK Health Security Agency, Colindale, London  {6} Public Health Programmes Directorate, UK H...

  Abstract Background :  Lassa fever (LF) is an acute viral hemorrhagic illness endemic to West Africa, with no licensed vaccines or targeted treatments available, highlighting a critical gap in global health preparedness. T cell-mediated immunity plays a central role in viral control and survival. Synthetic DNA vaccines offer a promising strategy to induce both humoral and cellular immunity against LF. Methods :  A Phase 1b, randomized, double-blind, placebo-controlled trial was conducted to assess the safety, tolerability, and immunogenicity of INO-4500 , a DNA vaccine encoding the Lassa virus (Josiah strain) glycoprotein precursor (GPC). A total of 220 healthy adults were randomized to receive either 1 mg or 2 mg of INO-4500 (intervention), or placebo, administered intradermally (ID) followed by electroporation (EP) at Day 0 and Week 4. Safety was evaluated through Week 48. Primary immunogenicity endpoints included humoral and cellular immune responses at multiple time...

  Summary Background Given the continued global circulation of monkeypox virus (MPXV), we aimed to assess the long-term clinical consequences of MPXV infection and the continued presence of the virus in saliva, semen, and the anorectum . We also aimed to compare long-term antibody dynamics after MPXV infection with modified vaccinia Ankara–Bavarian Nordic (MVA-BN) vaccination. Methods In this mixed retrospective and prospective cohort study, adults with acute MPXV infection at the Institute of Tropical Medicine (Antwerp, Belgium) were enrolled in a clinical registry (MPX-COHORT) from May 13, 2022, with follow-up at 1 month after infection. On Oct 3, 2022, we initiated a long-term follow-up study (POQS-FU-PLUS) to extend follow-up of people with mpox and to establish a parallel cohort of adults who received MVA-BN vaccination between Aug 3, 2022, and Jan 4, 2023. Participants were eligible for the second cohort if they received two doses of MVA-BN, unless they had previous smallpox ...

  Abstract Mucosal influenza vaccines may provide improved protection against infection and transmission , but their development is hindered by absence of immune correlates of protection . Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W805EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are...

  Abstract Background No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa . A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited. Methods In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly . Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural h...

  Summary Kyasanur Forest disease is a neglected tick-borne viral haemorrhagic fever endemic to India's Western Ghats , caused by the Kyasanur Forest disease virus , a flavivirus transmitted by Haemaphysalis spinigera ticks . The virus circulates in a sylvatic cycle among monkeys, rodents, shrews, birds, and ixodid ticks , and is transmitted to humans incidentally via tick bites . Since its discovery in 1957 in Karnataka , Kyasanur Forest disease has spread to other Indian states, driven by deforestation , forest fragmentation , and increased human incursion into wildlife habitats . Clinically, the disease manifests in a biphasic pattern , with haemorrhagic and neurotropic presentations . Although a formalin-inactivated vaccine is available , its efficacy is not promising, and no antivirals have been approved to date. Field reports indicate that mortality in monkeys might serve as an early indicator of forthcoming human outbreaks. The transmission dynamics of Kyasanur Forest diseas...

  Abstract Influenza is a global health concern, causing over 300,000 deaths worldwide annually . Current vaccines and natural infection mainly elicit antibodies against the variable head domain of the hemagglutinin (HA) glycoprotein. While these antibodies are highly neutralizing, the head domain constantly mutates due to selective pressure , causing the immune response to be strain-specific. Targeting the conserved HA stalk domain , however, has been shown to be a promising approach for a broadly protective vaccine . We previously demonstrated that presenting HA in an inverted orientation on virus-like particles (VLPs) significantly enhanced the induction of stalk-directed, cross-reactive antibodies compared to HA presented in a regular orientation. Here, we evaluated the protective efficacy of the inverted HA vaccine (VLP-HAinv) in mice against homologous, heterologous, and heterosubtypic influenza A virus challenges . VLP-HAinv vaccination in mice provided complete protection a...

  ABSTRACT An increase in the number of human cases of influenza A/H5N1 infection in the USA has raised concerns about the pandemic potential of the virus. Pre-existing population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody titers were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA-binding and neuraminidase-inhibiting antibody titers were comparable to those against a human A/H1N1 NA at baseline . Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1-n...

  September 2025   The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for influenza pandemic preparedness . Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture . National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production , clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.  Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes.  Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs. This document summarizes the antigenic and genetic c...

  Abstract Background :  Monitoring antigenic drift in human influenza A viruses is essential for vaccine strain selection and ensuring protection against circulating strains. Antigenic drift is traditionally assessed using ferret antisera , which provide monospecific responses , and human vaccinee sera , which reflect exposure to multiple antigens. In this study we evaluated the pig as an alternative source of antisera to study antigenic drift compared to immune responses in ferrets and humans. We included seasonal influenza A(H1N1pdm09) human viruses that had shown different antigenic characteristics when using ferret or human antisera.  Methods :  Pairs of pigs were inoculated with six human A(H1N1)pdm09 viruses circulating between 2019 and 2023, a period of marked antigenic drift. Pig and ferret antisera were analysed by hemagglutination inhibition (HI) and virus neutralization (VN) assays.  Results :  Pigs were successfully infected with all strains, s...