ETIDIOH - NEW

  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 ...

  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...

  Summary Background Chikungunya outbreaks have recurred in Brazil since 2014 . Building on earlier 28-day post-vaccination data , we now report 12-month safety and immunogenicity results of the VLA1553 vaccine in Brazilian adolescents. Methods In this double-blind, randomised, placebo-controlled, phase 3 trial , generally healthy adolescents aged 12–17 years were recruited at ten sites across Brazil. Individuals were excluded for immune-mediated or chronic arthritis or arthralgia, who are are immunologically compromised, or any recent live vaccines. Random allocation via simple block randomisation in a 2:1 ratio was stratified by baseline IgG and IgM serostatus by ELISA to receive a single intramuscular dose of VLA1553 or placebo . Assessed in the per-protocol population 28 days after vaccination, the primary endpoint was the proportion of baseline seronegative participants with chikungunya virus neutralising antibody levels assessed by a serum dilution achieving a 50% plaque redu...

  Abstract The unprecedented 2.3.4.4b. A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment . We assessed the pre-existing cross-reactive immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5–88 yrs) in multiple US geographic regions during 2021–2024. Pre-existing neutralizing and hemagglutinin (HA)-head- binding antibodies to A(H5N1) were low , but there were substantial cross-reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1). Antibodies to group 1 HA stalk were also prevalent and increased with age . A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies to A(H5N1) viruses but induced significant rise of functional NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies . Moreover, pre-pandemic stockpiled 2.3....

  Abstract Influenza remains a significant global public health concern. Live-attenuated influenza vaccines (LAIVs) are recognized as effective interventions for influenza prevention. Currently, two types of LAIVs are licensed for human use: one developed through cold-adapted viral gene mutation and the other through the deletion of the viral NS1 gene . However, the similarities and differences in these two LAIVs’ efficacy, safety, and immune responses have not been thoroughly studied. This study constructed a gene-deficient live-attenuated vaccine strain, CA4-dNS1, and a gene locus-mutated attenuated vaccine strain, CA4-cold , to compare their in vivo and in vitro replication capacity , broad-spectrum protective efficacy , safety, and immunogenicity . The results showed that both LAIVs provide comparable broad-spectrum protection against lethal H1N1 and H5N1 influenza challenges in mice and induce similar humoral and mucosal immune responses . Notably, the CA4-cold vaccine strain ...

  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...