MF59-adjuvanted A/Astrakhan #influenza #vaccine induces cross-neutralizing #H5N1 #antibodies in #ferrets against circulating clade 2.3.4.4b viruses

 

Abstract

The continued global spread of highly pathogenic avian influenza A(H5N1) viruses, particularly clade 2.3.4.4b, has increased zoonotic spillover risk and underscored the urgency of pandemic preparedness. Human vaccination is a key strategy for mitigating severe disease and limiting transmission, especially in a setting where avian influenza viruses pose a zoonotic threat. We evaluated the immunogenicity of the MF59-adjuvanted, egg-derived A/Astrakhan/3212/2020 (H5N8) influenza vaccine (CBER-RG8A) in ferrets. To assess cross-reactivity, we generated pseudoviruses bearing HA and NA from circulating A(H5N1) 2.3.4.4b viruses, including North American (B1.13 and D1.1) and Eurasian (DI.2) genotypes. Immunogenicity was assessed using hemagglutination inhibition and microneutralization assays. A single dose elicited robust neutralizing titers (GMT ≥ 160), while a second dose increased titers by ≥3.3-fold. Cross-reactivity was maintained across most strains; however, responses were reduced up to 8-fold against strains harboring the A156T HA mutation, which may introduce a glycosylation site at antigenic site B. Limited responses were detected against divergent clades, with modest titers against clade 2.3.2.1a. These findings suggest broad protection induced by the CSL Seqirus pandemic vaccine against contemporary clade 2.3.4.4b A(H5N1) viruses and underscore the value of ferret immunogenicity data in informing strain selection and regulatory preparedness when human clinical data are unavailable.

Source: 

Link: https://www.nature.com/articles/s41541-026-01438-4

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Current #status of #intranasal and inhaled #COVID19 #vaccines

 

Abstract

The COVID-19 pandemic has accelerated the development of intranasal and inhaled COVID-19. vaccines. Four vector-based and one adjuvanted protein-based vaccines have been licenced. They have been shown to be safe. However, their ability to induce strong protective mucosal immunity in humans remains to be improved. Diversifying intranasal vaccine platforms, improving the delivery of vaccine components and determining mucosal correlates of protection could help in optimizing intranasal COVID-19 vaccine efficacy.

Source: 

Link: https://www.nature.com/articles/s41541-026-01432-w

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Broad #protection against #Influenza A Viruses via an adjuvant-free #mucosal microparticle #vaccine with conserved CD8/CD4 bispecific peptides

 

Abstract

Influenza A viruses (IAVs) cause substantial global morbidity and mortality and are responsible for most known viral pandemics. Their rapid antigenic evolution enables escape from natural and vaccine-induced immunity, requiring annual vaccine reformulation, which offers limited breadth and variable effectiveness. Although a universal influenza vaccine remains a critical objective, most strategies have focused on conserved viral glycoproteins to elicit broadly neutralizing antibodies, with comparatively fewer efforts targeting conserved T cell antigens to achieve cross-subtype protection. Current T cell-based approaches often rely on individual CD8+ epitopes, which are limited by peptide instability, delivery constraints, and dependence on adjuvants. Here, we demonstrate a T cell-focused vaccine strategy that uses evolutionary consensus of IAV M1 and NP from the H1N1 and H3N2 subtypes to predict, map, and screen conserved regions enriched with multiple CD8+ and CD4+ epitopes. We selected the top-performing peptides from immunogenicity screening. We encapsulated them in polylactic-co-glycolic acid microparticles (PLGA-MPs) engineered for selective uptake by APCs and pH-dependent sustained release. Intranasal delivery of this vaccine formulation targeted the primary site of infection and induced robust mucosal immunity without the need for conventional adjuvants. Both human and murine influenza-experienced T cells mounted potent recall responses to the vaccine. In mice, immunization elicited strong CD8+ and CD4+ T cell responses and conferred broad protection against homologous H1N1 and H3N2 as well as heterologous H5N1 IAV subtypes. These findings collectively establish a mucosal, T cell-based vaccine platform that is adjuvant-free and capable of providing broad protection against IAV and other viruses with pandemic potential.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

DBT-ENDFLU, BT/IN/EU-INF/15/RV/19-20

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.29.715080v1

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Confirming #ERVEBO #Vaccination to Support #Ebola Virus #Surveillance

 

Abstract

Accurate confirmation of Ebola vaccination (ERVEBO) is essential for interpreting serologic data and assessing vaccine coverage during Ebola virus (EBOV) outbreaks. Current GP1,2-based assays cannot reliably distinguish vaccine-induced immunity from responses generated by natural infection. We developed a multiplex Luminex assay incorporating EBOV GP1,2, secreted glycoprotein (sGP), and a modified vesicular stomatitis virus nucleoprotein (VSV-P-N), a vector antigen encoded by ERVEBO but absent from wild-type EBOV. By using samples from US vaccinees and controls and a small comparison set from the Democratic Republic of the Congo, we found sGP and VSV-P-N demonstrated 100% sensitivity and >97.6% specificity for identifying vaccinees. In samples collected after a ring vaccination campaign in Guinea, combined sGP and VSV-P-N positivity confirmed vaccination in 94.8% of persons with written and 90.8% of persons with verbal confirmation of vaccination history. Our findings show that sGP and VSV-P-N provide a reliable signature of ERVEBO vaccination and support improved Ebola surveillance.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/4/25-1906_article

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A Live Attenuated #Vaccine Candidate against Emerging Highly Pathogenic #Cattle-Origin 2.3.4.4b #H5N1 [#Influenza] Viruses

 

Abstract

Influenza viruses present a significant public health risk, causing substantial illness and death in humans each year. Seasonal flu vaccines must be updated regularly, and their effectiveness often decreases due to mismatches with circulating strains. Furthermore, inactivated vaccines do not provide protection against shifted influenza viruses that have the potential to cause a pandemic. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b is prevalent among wild birds worldwide and is causing a multi-state outbreak affecting poultry and dairy cows in the United States (US) since March 2024. In this study, we have generated a NS1 deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1, namely LPhTXdNS1, and validated its safety, immunogenicity, and protection efficacy in a prime vaccination regimen against wild-type (WT) A/Texas/37/2024 H5N1. The attenuation of LPhTXdNS1 in vitro was confirmed by its reduced replication in cultured cells and inability to control IFNβ promoter activation. In C57BL/6J mice, LPhTXdNS1 has reduced viral replication and pathogenicity compared to WT A/Texas/37/2024 H5N1. Notably, LPhTXdNS1 vaccinated mice exhibited high immunogenicity that reach its peak at weeks 3 and 4 post-immunization, leading to robust protection against subsequent lethal challenge with WT A/Texas/37/2024 H5N1. Altogether, we demonstrate that a single dose vaccination with LPhTXdNS1 is safe and able to induce protective immune responses against H5N1. Both safety profile and protection immunity suggest that LPhTXdNS1 holds promise as a potential solution to address the urgent need for an effective vaccine in the event of a pandemic for the treatment of infected animals and humans.

Competing Interest Statement

The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and NovavaxA.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. All other authors declare no commercial or financial conflict of interest.

Source: 

Link: https://www.biorxiv.org/content/10.1101/2025.03.28.646033v2

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Three decades of #discovery: An overview of #Hendra virus, the original #Henipavirus

 

Abstract

Hendra virus (HeV) emerged in Australia in 1994, causing a devastating outbreak among horses in Brisbane with spread to humans, resulting in one death. This nonsegmented, negative-stranded RNA virus belongs to the family Paramyxoviridae and represents the first zoonotic paramyxovirus isolated from bats. Flying foxes (genus Pteropus) serve as the natural reservoir, with all four mainland Australian species carrying antibodies with no apparent disease. HeV initiates infection by binding ephrin-B2 receptors on vascular endothelial cells, driving characteristic pathology involving vasculitis, thrombosis, and neurological complications. Horses are amplifying hosts, shedding virus abundantly in respiratory secretions and posing transmission risks to humans during invasive procedures. To date, seven confirmed human infections have been documented, with a 57% fatality rate, presenting as severe respiratory disease or progressive encephalitis. Two genetic variants are now recognized: the original HeV genotype 1 and the emerging HeV genotype 2, identified in limited equine cases. Recent surveillance of bat roosts revealed substantial viral diversity, with peak shedding occurring during winter—coinciding with equine spillover peaks. Prevention integrates multiple strategies: the licensed equine vaccine Equivac which provides One Health protection for both horses and human contacts; biosecurity measures including proper PPE; and habitat restoration to reduce nutritional stress in bat populations. Emerging therapeutics include monoclonal antibodies, with m102.4 showing cross-protective activity against both HeV and the closely related Nipah virus. No licensed human vaccines currently exist, though candidates are in development. Future prevention strategies increasingly recognize the importance of Indigenous-led conservation approaches alongside biomedical interventions. This review will focus on the history of HeV, virus replication and diversity, epidemiology, clinical manifestations, diagnosis, treatment, prevention, as well as ecological and interdisciplinary countermeasures.

Author summary

Hendra virus (HeV) was first detected in 1994, with two outbreaks occurring within 2 months of that year. One was the index outbreak in the Brisbane suburb of Hendra, and the other was retrospectively diagnosed in the following year. This review examines the discoveries that have been made in the 30 years since its discovery.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014138

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Defining #influenza-specific B cells in #vaccine #responders, non-responders and influenza breakthrough #infections

 

Abstract

Although seasonal influenza vaccination programs are effective at a population level, our data from inactivated influenza vaccine (IIV) cohorts in years 2015-2022 reveal that 50-60% of individuals do not seroconvert following immunization. The underlying mechanisms of vaccine non-responsiveness are far from understood. In this study, we sought to define key determinants of optimal B cell immune responses elicited by seasonal influenza vaccination, and to explore why some individuals fail to elicit humoral immunity following immunization. Immune responses associated with seroconversion and vaccine failure from individuals immunized with IIVs were compared at cellular and molecular levels using single-cell transcriptomics. We analyzed HA-specific B cell immunity across vaccine-responders, breakthrough infections and patients hospitalized with acute influenza. Droplet-based single-cell RNA sequencing and VDJ-sequencing of influenza-specific B cells from stored PBMCs was performed using 10x Genomics. Our results show that atypical B cells are the major subset of B cell responses in vaccine non-responders on day 28 post-vaccination. Conversely, individuals who seroconvert had diverse B cell phenotypes. The use of recombinant influenza-specific HA probes allowed us to dissect expression patterns on influenza HA-specific B cells. We found that HA-specific B cells of vaccine non-responders for A/H1N1 and A/H3N2 components displayed elevated atypical-like markers (CD11c, FcRL-5) at baseline, compared to responders. Analysis of differentially expressed genes (DEGs) between responders and non-responders identified differential expression of HLA-DR, CD74, CD83, and CXCR3 genes. We subsequently demonstrated reduced frequencies of HLA-DR-, CD74- and CD83-expressing B cells in patients hospitalized with influenza, compared to healthy participants. Hospitalized influenza patients also had significantly higher proportions of atypical CD21-CD27- B cells. Overall, our data demonstrate an association between elevated frequencies of atypical-like B cells with both lack of seroconversion following immunization and severe influenza infection. These findings broaden our understanding of humoral immunity in influenza vaccination and infection, providing novel insights for vaccination strategies and design.

Competing Interest Statement

Katherine Kedzierska has received paid honoraria from Pfizer. Hayley McQuilten has a consultancy role for Ena Therapeutics

Funder Information Declared

NHMRC

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.19.710321v1

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#UK, #England: Expansion of #Meningitis B #vaccination offer to #Kent #Students (UKHSA, March 19 '26)

 

The Meningitis B vaccine will now be offered to everyone who has been offered preventative antibiotic treatment as part of this outbreak.

-- Vaccination will now be extended to everyone who has been offered preventative antibiotic treatment as part of this outbreak.

-- Preventative antibiotics – and vaccination – will also now be offered to the 6th form students (years 12 and 13) in schools and colleges in Kent where confirmed or probable cases are identified.

-- On a case-by-case basis, future risk assessment may also support use in other year groups or settings.

-- Students can, and should, continue to attend schools and colleges as normal. 

-- The NHS Kent and Medway website will be updated shortly with vaccination sites for those eligible.

-- The key intervention to protect people and halt the spread remains for people to come forward for antibiotic treatment. A single course of antibiotics is highly effective in preventing the contraction and spread of this disease in 90% of cases.

-- As a further precautionary measure, we are extending the offer of antibiotic prophylaxis and vaccine to any individuals who attended Club Chemistry from the 5 March until it closed voluntarily on 15 March.

-- 20,000 vaccines from the NHS supply will be made available to the private market, to ease current demand experienced by pharmacies. These will enter the private market within around 48 hours.

In response to the ongoing Meningitis B (MenB) outbreak in Kent, the UK Health Security Agency (UKHSA) is expanding the offer of preventative antibiotic treatment and vaccination to control the outbreak. 

Preventative antibiotic treatment and vaccination will now be offered to 6th sixth form students (years 12 and 13) in schools and colleges in Kent with confirmed or probable cases On a case-by-case basis, following risk assessment by the local health protection team, antibiotics and vaccination may also be made available to additional year groups. Students can, and should, continue to attend schools and colleges as normal.

In addition to the approximately 5,000 students who were initially contacted, vaccination will now be extended to everyone who has been offered preventative antibiotic treatment as part of this outbreak. This includes University of Kent students who live on the Canterbury Campus and other relevant halls of residence; close contacts of confirmed or suspected cases, and students in four education settings in Kent where cases have been confirmed. Anyone who visited Club Chemistry in Canterbury between 5 and 15 March will also be offered a vaccine and antibiotics as a precaution after one suspected case revisited the nightclub before it shut voluntarily.

This extension ensures that those most likely to have been in close contact with confirmed or suspected cases are offered longer term protection as early as possible.

The NHS Kent and Medway website will be updated shortly with vaccination sites for those eligible.

Patients eligible for antibiotics will now be able to request a vaccination and antibiotics from their local GP immediately – wherever they are in England.

While preventative antibiotics remain the key intervention to protect people and halt the spread of infection, vaccination is being offered as an additional measure to provide longer term protection for those at increased risk.

Given current demand on the private MenB vaccine market, 20,000 doses will also be released from NHS supply to support continuity of private provision, enabling up to 2,000 pharmacies to receive vaccines in the next 48 hours.

Professor Susan Hopkins, Chief Executive of the UK Health Security Agency, said: 

''By extending the vaccination programme to everyone who has been offered preventative antibiotics, we are taking an important additional step to protect those most likely to have been exposed. The message is simple: if you have had the antibiotic, you are also eligible for the vaccination.

People are reminded to remain alert to the signs and symptoms of invasive meningococcal disease and to seek urgent medical attention if they or someone they know becomes unwell.

Background 

Meningococcal disease (meningitis and sepsis) is an uncommon but serious disease caused by meningococcal bacteria. Very occasionally, the meningococcal bacteria can cause serious illness, (inflammation of the lining of the brain) and sepsis (blood poisoning), which can rapidly lead to sepsis. 

The onset of illness is often sudden and early diagnosis and treatment with antibiotics are vital. 

Early symptoms, which may not always be present, include: 

- a rash that doesn’t fade when pressed with a glass

- sudden onset of high fever

- severe and worsening headache

- stiff neck

- vomiting and diarrhoea

- joint and muscle pain

- dislike of bright lights

- very cold hands and feet

- seizures

- confusion/delirium

- extreme sleepiness/difficulty waking

Young people going on to university or college for the first time are particularly at risk of meningitis because they newly mix with so many other students, some of whom are unknowingly carrying the bacteria at the back of their nose and throat. 

There are numerous strains of the meningococcal infection.

There are numerous strains of the meningococcal infection. The MenACWY vaccination gives good protection against MenA, MenC, MenW, and MenY and is routinely offered to teenagers in school Years 9 and 10. However, this vaccine does not protect against all forms of meningococcal infection. Other strains such as MenB can circulate in young adults, which is why it’s important to know how to spot the symptoms of meningitis and sepsis as early detection and treatment can save lives. 

Further information on meningococcal disease 

Meningitis, The Meningitis Research Foundation, Monday to Friday, 9am to 5pm, UK: 080 8800 3344  -  Republic of Ireland: 1800 41 33 44  

Meningitis Now - 0808 80 10 388 (9am to 4pm Monday to Thursday and 9am to 1pm Friday)

Source: 

Link: https://www.gov.uk/government/news/expansion-of-meningitis-b-vaccination-offer-to-kent-students

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#UK, #England: Cases of invasive #meningococcal #disease notified in #Kent (UKHSA, March 16 '26)

 

From: UK Health Security Agency

Published: 16 March 2026

Last updated: 16 March 2026 

Update 16 March

The UK Health Security Agency (UKHSA) is continuing to investigate an outbreak of meningococcal disease in Kent with 13 cases notified since 13 March. Sadly, this includes 2 people who are known to have died.

Investigations have confirmed some of the cases visited Club Chemistry in Canterbury between 5 to 7 March prior to becoming unwell. UKHSA’s health protection team is working closely with the nightclub and partners including the University of Kent to limit the spread.

UKHSA is now advising anyone who visited Club Chemistry on 5 March, 6 March or 7 March to come forward for preventative antibiotic treatment as a precautionary measure. 

This can be collected from the following sites:

-- Senate Building at University of Kent, CT2 7NZ – open until 8pm on Monday 16 March (queue closes 7.15pm) and from 9am to 8pm on Tuesday 17 March.

-- Gate Clinic, Kent and Canterbury Hospital, Ethelbert Road, Canterbury, CT1 3NG - open until 8pm on Monday 16 March and planned to open from 8.30am to 7.30pm on Tuesday 17 March.

-- Westgate Hall, Westgate Hall Road, Canterbury, Kent, CT1 2BT. Planned to be open from 8.30am to 7.30pm on Tuesday 17 March.

-- Carey Building, Thanet Hub, Margate Northwood Rd, Westwood, Broadstairs, CT10 2WA. Planned to be open from 8.30am to 7.30 pm on Tuesday 17 March.

Advice has been issued to 16,000 staff and students at the University of Kent, where antibiotics are also being offered to those who need them.

Meningococcal disease can progress rapidly. Signs and symptoms of meningococcal meningitis and septicaemia can include:

- a fever, 

- headache, 

- rapid breathing, 

- drowsiness, 

- shivering, 

- vomiting, and 

- cold hands and feet. 

Septicaemia can also cause a characteristic rash that does not fade when pressed with a glass.

Early symptoms can often be confused with other illnesses such as a cold, flu or hangover, and students are particularly at risk of missing the early warning signs. If you or anyone you know develops any of these symptoms, seek medical help immediately by contacting a GP, calling NHS 111 or dialling 999 in an emergency. Knowing the signs and taking early treatment can be lifesaving.

Trish Mannes, UKHSA Regional Deputy Director for the South East, said:

''Our thoughts remain with the friends and family involved and we understand that many people in the university and wider community will be affected by this sad news.

''Our investigations have identified that some cases visited Club Chemistry in Canterbury and it is important that anyone who visited the club between 5 and 7 March now comes forward for preventative antibiotic treatment as a precaution, as well as those offered antibiotics at the university – these students are being contacted directly through the university.

''If you think you may have symptoms of meningitis, do not hesitate to seek medical help by contacting your GP or calling NHS 111.

Background

Meningococcal disease (meningitis and septicaemia) is an uncommon but serious disease caused by meningococcal bacteria. Very occasionally, the meningococcal bacteria can cause serious illness, (inflammation of the lining of the brain) and septicaemia (blood poisoning), which can rapidly lead to sepsis.

The onset of illness is often sudden and early diagnosis and treatment with antibiotics are vital.

Early symptoms, which may not always be present, include:

- a rash that doesn’t fade when pressed with a glass

- sudden onset of high fever

- severe and worsening headache

- stiff neck

- vomiting and diarrhoea

- joint and muscle pain

- dislike of bright lights

- very cold hands and feet

- seizures

- confusion/delirium

- extreme sleepiness/difficulty waking

Young people going on to university or college for the first time are particularly at risk of meningitis because they newly mix with so many other students, some of whom are unknowingly carrying the bacteria at the back of their nose and throat.

There are numerous strains of the meningococcal infection. The MenACWY vaccination gives good protection against MenA, MenC, MenW, and MenY. It is routinely offered to teenagers in school Years 9 and 10. However, this vaccine does not protect against all forms of meningococcal infection. Other strains such as MenB can circulate in young adults, which is why it’s important to know how to spot the symptoms of meningitis and septicaemia as early detection and treatment can save lives. 

Source: 

Link: https://www.gov.uk/government/news/cases-of-invasive-meningococcal-disease-confirmed-in-kent

____

#Glycoprotein-specific transcriptional response contributes to differential #vaccine #protection against lethal #Ebola virus #infection

 

Abstract

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 107 PFU to provide broader population protection. Identification of a protective lower dose providing rapid protection would ease supply burdens during future outbreaks and enhance vaccine coverage. We previously generated a VSV-based vaccine expressing the glycoprotein of the Makona variant (VSV-Mak) which provided complete protection against homologous challenge 28 DPV at as low as 1 × 101 PFU. However, the transcriptional responses engendered by VSV-Mak and VSV-Kik vaccines in the context of early EBOV-Makona challenge have not yet been evaluated. In the current study, we compared transcriptional responses following a low dose (1 × 104 PFU) of lab-grade VSV-Mak or GMP-grade VSV-Kik and subsequent EBOV-Makona challenge 10 DPV. VSV-Kik provided complete protection against heterologous challenge and elicited rapid antiviral transcriptional changes followed by the activation of adaptive immunity. On the other hand, VSV-Mak only provided partial protection and induced minimal transcriptional response. These results highlight a glycoprotein-specific transcriptional response after vaccination despite the high EBOV variant homology.

Source: Vaccine, https://www.sciencedirect.com/journal/vaccine/vol/79/suppl/C

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26002185?via%3Dihub

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Interim Estimates of 2025–26 Seasonal #Influenza #Vaccine #Effectiveness — #USA, September 2025–February 2026 (CDC MMWR)

 

Abstract

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025–26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness–associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025–26 influenza season, using a test-negative case-control design. Among children and adolescents aged <18 years, VE was 38%–41% against influenza outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%–34% against influenza outpatient visits and 30% against influenza-associated hospitalization. Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings. Among children and adolescents, VE against influenza A(H3N2)–associated outpatient visits was 35% and against influenza A(H3N2)–associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%–71% among children and adolescents and was 63% among adults. Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025–26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

Source: 

Link: http://dx.doi.org/10.15585/mmwr.mm7509a2

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Immunogenicity and #safety of MVA-BN #vaccine administered 5 years after a two-dose primary series in #DRC: a prospective cohort study

 

Summary

Background

The expanding mpox outbreak in Africa and travel-associated cases in other continents have increased efforts to vaccinate populations at high risk. This study aimed to assess serological immune responses 5 years after individuals received a primary vaccination (two-dose series) with the smallpox and mpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN), as well as to evaluate the safety and immunogenicity of a third dose (booster). To date, there are no data for immunological memory or third-dose-induced immunity for MVA-BN at these long-term timescales.

Methods

In this open-label, prospective cohort extension, we re-enrolled health-care workers from a 2017 vaccination study in Bokungu Health Zone, DR Congo, to receive a third dose of MVA-BN. All previous participants were offered the opportunity to re-enrol. Participants were grouped according to whether they had received a childhood smallpox vaccination with a replication-competent vaccine strain (historically vaccinated group) or had no history of smallpox vaccination (historically naive group). Participants were excluded from serological analyses if they had any history of mpox or mpox-like lesion-presenting illness, if their previous vaccination status during initial enrolment for the primary series was unknown, or if they had discordant vaccination information. The coprimary outcomes were sustained humoral immunity following primary vaccination with MVA-BN (5 years previously) and the immunogenicity and safety of the booster vaccination. Safety was analysed in patients with a completed immediate adverse event form or adverse event diary. Adverse events were assessed on days 0 (within 30 min of the booster), 7, and 14. Antibody responses were measured by ELISA, plaque reduction neutralisation tests, and endpoint titre at re-enrolment (day 0, before administration of the booster dose) and on days 7, 14, and 545 after the booster dose.

Findings

Between Sept 7 and 15, 2022, 170 (66·1%) of 257 Bokungu health-care personnel vaccinated in 2017 were re-enrolled to receive a third (booster) dose of MVA-BN. At re-enrolment, low levels of circulating antibody were observed, but 30 (61%) of 49 historically naive participants and 95 (96%) of 99 historically vaccinated participants with childhood smallpox vaccination remained seropositive 5 years after the primary MVA-BN two-dose series. After the third dose, there was a rapid and massive increase in anti-orthopoxvirus IgG but not IgM, and a 93-fold rise in orthopoxvirus neutralising antibody titres was observed by day 14 in historically naive participants, irrespective of participants' seropositivity at the time of booster vaccination. The third dose resulted in enhanced durability of circulating antibody concentrations, with endpoint titres on day 545 remaining more than six-fold higher than day 0 values. There was a greater risk of local reactogenicity after the booster dose than after the primary vaccination (relative risk 4·2, 95% CI 2·81–6·46), but there was no difference in the risk of systemic adverse events up to day 7 after vaccination. No grade 3 serious adverse events were recorded after booster dose administration.

Interpretation

These data show that primary MVA-BN vaccination induces sustained immunological memory up to 5 years after vaccination and that a booster dose strongly enhances circulating antibody levels and durability. Future studies should clarify the role of circulating antibody concentrations as a correlate of protection from monkeypox virus infection.

Funding

US Centers for Disease Control and Prevention and US Biomedical Advanced Research and Development Authority.

Translation

For the French translation of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00001-0/fulltext?rss=yes

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#Vaccine-Elicited #Antibody Responses to #Influenza #H3N2 Subclade K

 

{Excerpt}

(...)

Results

NAb geometric mean titers against H1N1 WI/22, H3N2 BA/22, H3N2 CR/23, H3N2-K BA/25, and H3N2-K NY/25 were 200, 231, 119, 50, and 60 at baseline and increased to 582, 661, 356, 85, and 119 at peak immunogenicity, respectively (...), reflecting a significant 2.86- to 2.99-fold increase in NAb titers against the prior H1N1 and H3N2 strains but a lower 1.70- to 1.98-fold increase in NAb titers against the H3N2-K strains. Baseline antibody titers to the H3N2-K strains were 2.0- to 4.6-fold lower than to the prior H1N1 and H3N2 strains (P < .001), and peak antibody titers to the H3N2-K strains following vaccination were 3.0- to 7.8-fold lower than to the prior H1N1 and H3N2 strains (P < .001).

(...)

Source: 

Link: https://jamanetwork.com/journals/jama/fullarticle/2846268?guestAccessKey=10f1c0a1-4189-438d-9f71-a588fdd0db53&utm_medium=email&utm_source=postup_jn&utm_campaign=article_alert-jama&utm_content=olf-tfl_&utm_term=030926#250858592

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#Report of the 49th meeting of #WHO Global Advisory #Committee on #Vaccine #Safety 27–28 November 2025 (Excerpt, Mar. 6 '26)

 

{Excerpt}

(...)

COVID-19 current vaccine safety status and insights 

-- Since 2021, GACVS has regularly reviewed the safety of COVID-19 vaccines, including through global pharmacovigilance data and dedicated reviews of myocarditis, pregnancy outcomes and other adverse events of special interest (AESI). 

-- The most recent updates reaffirmed that the benefits of vaccination outweigh the risks across all groups and advised continued monitoring for younger males and follow-up of persons who have reported vaccine-associated myocarditis. 

-- Many individuals have received three or more doses of COVID-19 vaccine. 

-- Some adverse events – such as myocarditis – seem to occur mainly after the second dose of mRNA COVID- 19 vaccines. 

-- However, the outcomes were less severe in persons who developed myocarditis after vaccination compared to those unvaccinated and following infections, including SARS- CoV-2. 

-- Also, children under six months of age seem to be at higher risk of severe COVID-19 infection along with people over the age of 65 years. 

-- WHO has recommended continued vaccination for high-priority groups while acknowledging that gaps remain in the evidence on the safety of repeated dosing, long-term outcomes, and in subgroups such as children and pregnant women. 

-- As of October 2025, for all COVID-19 vaccines, there were only 32 cases of perturbation of fetal development in EudraVigilance, of which most were reported with the original vaccine strains. 

-- An analysis of safety of protein-based COVID-19 vaccines by the Uppsala Monitoring Centre (UMC) showed that as of November 2025 there were almost 6 million reports for all COVID-19 vaccines in UMC’s VigiBase. 

-- Of these, 16 548 reports concerned updated COVID-19 vaccine variants; among these were 5085 reports for updated protein-subunit vaccines. 

-- Around 17.4% of these were serious, and 50 reported a fatal outcome. 

-- Most reports were for the variant NVX CoV 2373 and most deaths were older vaccinees aged 75 years or more. 

-- GACVS reviewed findings from the Scandinavian collaboration called SCOPE (Scandinavian studies of COvid-19 in PrEgnancy). 

-- Findings showed no increased risk of adverse pregnancy, maternal or neonatal outcomes after mRNA COVID-19 vaccination in pregnancy in Denmark, Norway and Sweden. 

-- As of September 2025, the recommendation for vaccination in pregnancy was revised to apply only to specific high-risk groups. 

-- A case-control study by SCOPE of all women with a miscarriage before 14 weeks and all women with a primary care-based confirmation of an ongoing pregnancy in the first trimester revealed no evidence of increased risk of early pregnancy loss after COVID-19 vaccination. 

-- A further investigation of COVID-19 infection and vaccination with mRNA vaccines during the first trimester of pregnancy and the risk of congenital anomalies, in a population-based cohort of 150 000 live-born infants in Denmark, Norway and Sweden, showed no increased risk of major congenital anomalies among infants whose mothers were vaccinated against COVID-19 during the first trimester. 

-- A SCOPE investigation of the association between COVID-19 vaccination and several pregnancy outcomes among a cohort of almost 160 000 singleton pregnancies between January 2021 and 2022 in Norway and Sweden showed that vaccination against COVID-19 during pregnancy was not associated with any of the studied adverse pregnancy outcomes. 

-- In another SCOPE study of COVID-19 vaccination during pregnancy and the risk of severe postpartum haemorrhage, including more than 300 000 single-term deliveries in Denmark, Norway and Sweden, no evidence was found of an association between COVID-19 vaccination at any time during pregnancy and severe postpartum hemorrhage. 

-- Finally, SCOPE investigated neonatal outcomes after COVID-19 vaccination with mRNA vaccine during pregnancy in a cohort of almost 200 000 infants in Norway and Sweden. 

-- Again, no increased odds were found of any adverse neonatal outcomes and neonatal mortality. 

-- In consideration of the evidence presented, GACVS members agreed the following: 

- Repeated-dose safety (including boosters with variant-containing vaccines): 

* Current evidence remains reassuring, with no new safety signals recently identified. 

- Safety of protein-based vaccines: 

* While generally well tolerated, reported adverse events include a proportion of serious individual case safety reports (ICSRs) in the global database. Several potential signals (e.g. tinnitus, antibody-dependent enhancement, thrombosis) require further evaluation. Additional data collection and analysis are therefore recommended to strengthen the evidence base for these vaccines. 

- Long-term outcomes of known risks (e.g. myocarditis, pregnancy outcomes): 

* Myocarditis continues to occur predominantly in younger adults, typically with mild-to- moderate severity and most frequently after the second dose. Longer follow-up studies are needed to define the long-term prognosis and risks of revaccination in affected individuals. 

- Subgroup-specific safety (children, young males, older adults, immunocompromised individuals, pregnant women): 

* Evidence to date shows no harmful effects of mRNA COVID-19 vaccination during pregnancy, including no increase in congenital anomalies, adverse perinatal outcomes, or some post-natal complications. Some studies even suggest lower odds of intracranial haemorrhage, cerebral ischaemia and neonatal mortality among infants of vaccinated mothers. 

- Safety monitoring during the transition to endemic COVID-19 vaccination: 

* Continued vigilance is required, particularly regarding more recent variant-adapted vaccines which remain safe on the basis of current data. Enhanced monitoring of protein-based vaccines is important given the comparatively limited evidence and the presence of identified risks that warrant further investigation.

(...)

Source: 

Link: https://www.who.int/publications/journals/weekly-epidemiological-record

____

Optimizing an avian #influenza #vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 #adjuvant

 

Abstract

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime–boost model. Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its potential as an adjuvant for next-generation influenza vaccines while underscoring the need for further optimization to achieve true cross-neutralizing protection.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709477v1

____

Stabilization of the #H5 clade 2.3.4.4b #hemagglutinin improves #vaccine-elicited neutralizing #antibody responses in mice

 

Abstract

Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo–electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA–lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA–stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.

Source: 

Link: https://www.science.org/doi/10.1126/scitranslmed.aea8770

____

Evaluation of an #H5 #influenza virus #mRNA-lipid nanoparticle (LNP) #vaccine in lactating dairy #cows

 

Abstract

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.

Competing Interest Statement

S.E.H. and D.W. are co-inventors on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins and as a vaccine platform. D.W. is also named on patents describing the use of lipid nanoparticles and lipid compositions for nucleic acid delivery. S.E.H. reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. JDB consults for Apriori Bio, Invivyd, GSK, Pfizer, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to viral deep mutational scanning.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, 75N93021C00015

United States Department of Agriculture, https://ror.org/01na82s61, 5030-32000-231-000-D, 3200-231-112-I

United States Department of Energy, https://ror.org/01bj3aw27, DE-AC05-06OR23100

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709308v1

____

#Development and Characterization of Candidate #Vaccine #Viruses against High Pathogenicity Avian #Influenza #H5 Viruses for Rapid #Pandemic Response

 

Abstract

High pathogenicity avian influenza A(H5) viruses pose a pandemic threat. These viruses have rapidly evolved in birds and frequently crossed species barriers, resulting in over 1,000 confirmed human infections, with a case fatality proportion of approximately 50%. In response, the U.S. CDC has developed dozens of A(H5) candidate vaccine viruses (CVVs) over the past two decades, primarily targeting clades known to infect humans. This report summarizes the development and characterization of the CVVs, with a particular focus on their antigenic relationships with clades 2.3.2.1e and 2.3.4.4b A(H5N1) viruses, which have been responsible for the majority of recent human infections.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag132/8502029

____

Recommended #composition of #influenza virus #vaccines for use in the 2026 – 2027 northern hemisphere influenza season (#WHO, Feb. 27 '26)

 

February 2026 

WHO convenes technical consultations {1} in February and September each year to recommend viruses for inclusion in influenza vaccines {2} for the northern hemisphere (NH) and southern hemisphere (SH) influenza seasons, respectively. 

This recommendation relates to the influenza vaccines for use in the NH 2026-2027 influenza season. 

A recommendation will be made in September 2026 relating to vaccines that will be used for the SH 2027 influenza season. 

WHO guidance for choosing between the NH and SH formulations for countries in tropical and subtropical regions is available on the WHO Global Influenza Programme website {3}.  

National or regional authorities approve the composition and formulation of influenza vaccines used in each country. 

National public health authorities are responsible for making recommendations regarding the use of the vaccine. 

WHO has published recommendations on the prevention of influenza {4}.  

Seasonal influenza activity 

From September 2025 through January 2026, influenza activity was reported in all transmission zones. 

Overall influenza virus detections were higher compared to the same reporting period in 2024-2025 but peaked in December 2025 for this recent period compared to February 2025 for the previous period. 

During this reporting period, influenza A viruses predominated, although the proportion of virus detections varied among transmission zones. 

In Africa, influenza activity increased during the start of the reporting period, with a predominance of influenza A viruses in all transmission zones. 

In Eastern, Northern, and Western Africa, among subtyped influenza A viruses, A(H1N1)pdm09 viruses accounted for the majority of detections early in the reporting period while A(H3N2) viruses predominated later in the reporting period. 

Influenza detections peaked in November in Western Africa and December in Eastern and Northern Africa. 

In Middle Africa, influenza detections remained low throughout the reporting period with a slight predominance of A(H1N1)pdm09 viruses early in the reporting period. 

In Southern Africa, influenza detections remained low throughout the reporting period, with a predominance of influenza A viruses. 

In Northern and Middle Africa, there was low and sustained influenza B activity throughout the reporting period. 

In Asia, influenza activity increased during the start of the reporting period in South East and Western Asia, from October in Central and Eastern Asia, and from November in Southern Asia, with a predominance of influenza A viruses in all transmission zones. 

Most influenza detections were reported from Eastern Asia, where activity peaked in early December. 

In Southern Asia, influenza activity also peaked in December; in Central Asia influenza activity peaked in November, and in Western and South East Asia, influenza activity peaked in October. 

Among subtyped influenza A viruses, A(H3N2) viruses accounted for the majority of detections in all transmission zones; detections of A(H1N1)pdm09 and influenza B viruses remained low in most transmission zones throughout the reporting period, except in Eastern Asia where there was a substantial rise in influenza B viruses in recent weeks. 

In Europe, influenza activity increased from mid-September in Northern Europe, from October in South West Europe and from mid-November in Eastern Europe, with a predominance of influenza A viruses in all transmission zones. 

Influenza detections peaked in December in Northern and South West Europe but remained elevated through January. 

Influenza detections continued to increase through January in Eastern Europe. 

Among subtyped influenza A viruses, A(H3N2) viruses predominated. 

In South West Europe, detections of A(H1N1)pdm09 viruses slightly increased in mid-November. 

In Eastern and Northern Europe, detections of A(H1N1)pdm09 and influenza B viruses remained low throughout the reporting period.  

In the Americas, influenza activity increased from the start of the reporting period in Temperate and Tropical South America and from November in North America and Central America Caribbean. 

Influenza A viruses accounted for most detections, and influenza B virus detections remained low throughout the reporting period in all transmission zones, except in North America where there was a substantial rise in influenza B viruses in recent weeks. 

In North America, activity peaked in late December. 

Among subtyped influenza A viruses, there was a predominance of A(H3N2) viruses. 

In Central America Caribbean, influenza activity remained elevated through mid-January with A(H3N2) virus detections predominant from December. 

In Tropical South America, influenza activity peaked in early November and slowly declined until the end of the reporting period. 

Among subtyped influenza A viruses, A(H3N2) predominated through November then co-circulated at similar proportions to A(H1N1)pdm09 until the end of the reporting period. 

In Temperate South America, influenza activity peaked in mid-November and among subtyped influenza A viruses, A(H3N2) viruses predominated throughout the reporting period.  

In Oceania, influenza activity decreased until mid-October, increased in December and decreased since mid-December. A(H1N1)pdm09 and B viruses were detected at similar levels until mid-September and A(H3N2) virus detections predominated since then. 

Influenza A 

Globally, influenza A virus detections greatly outnumbered those of influenza B. 

Among subtyped influenza A viruses, A(H3N2) viruses predominated throughout the reporting period in most transmission zones. 

In Eastern, Northern, Western Africa, Central America Caribbean and Oceania, influenza A(H1N1)pdm09 virus detections predominated during the first part of the reporting period, and A(H3N2) virus detections predominated in the latter part of the reporting period. 

Influenza A(H1N1)pdm09 virus detections increased slightly towards the latter part of the reporting period in Eastern and South West Europe, Central America Caribbean and Tropical South America. 

The overall number of influenza detections was low in Middle and Southern Africa. 

Influenza B 

Globally, influenza B virus detections remained low throughout the reporting period. 

Increases in influenza B virus detections in January were reported in North America and Eastern Asia. 

All influenza B viruses where lineage was confirmed belonged to the B/Victoria lineage. 

(...)

Zoonotic influenza  

From 23 September 2025, sporadic zoonotic influenza infections were reported, in most cases, following exposure to infected birds, swine or contaminated environments. 

Single cases of A(H5N1) from Bangladesh, A(H5N2) from Mexico, and A(H5N5) from the United States of America were reported. 

Three A(H5N1) cases were reported from Cambodia. 

Fourteen cases of A(H9N2) and one case of A(H10N3) were reported from China. 

Single cases of A(H1N1)v and A(H1N2)v were reported from China, a case of A(H1N2)v from the United States of America, and a case of A(H3N2)v from Brazil. 

Genetic and antigenic characteristics of recent seasonal influenza viruses, human serology and antiviral susceptibility 

Influenza A(H1N1)pdm09 viruses  

Since September 2025, A(H1N1)pdm09 viruses circulated globally, but did not predominate in any region. 

The haemagglutinin (HA) genes of viruses that were genetically characterized belonged to the 5a.2a and 5a.2a.1 clades. 

Viruses from clade 5a.2a subclades C.1, C.1.9 and C.1.9.3 circulated in low numbers, with the largest proportion of detections in Africa {5}. 

Since September 2025, clade 5a.2a.1 subclades D.3.1 and D.3.1.1 viruses circulated globally. 

The D.3.1 subclade with substitutions T120A, I372V, I460T and V520A predominated in Western Pacific, Africa, South East Asia and several countries in the Americas. 

D.3.1.1 viruses characterized by R113K and more recently acquired substitutions A139D, E283K and K302E predominated in some countries in Europe, the Middle East and North America. 

The antigenic properties of A(H1N1)pdm09 viruses were assessed in haemagglutination inhibition (HI) assays with post-infection ferret antisera. 

HI results for viruses with collection dates since September 2025 showed that ferret antisera raised against cell culture-propagated A/Wisconsin/67/2022-like and eggpropagated A/Victoria/4897/2022-like viruses from the 5a.2a.1 clade recognized viruses in both 5a.2a and 5a.2a.1 clades well. 

However, post-infection ferret antisera raised against viruses from clade 5a.2a showed some reduction in recognition of the now predominating D.3.1 and D.3.1.1 subclade viruses. 

Post-infection ferret antisera raised against viruses from subclade D.3.1 (e.g., A/Missouri/11/2025) recognized recently circulating viruses from both 5a.2a and 5a.2a.1 clades well.  

Human serology studies used 15 serum panels from children, adults (18 to 64 years) and older adults (≥65 years) who had received egg-propagated inactivated (standard, high dose or adjuvanted), cell culture-propagated inactivated or recombinant trivalent or quadrivalent vaccines with NH 2025-2026 influenza vaccine formulations. 

-- NH 2025-2026 egg-based vaccines contained A/Victoria/4897/2022 (H1N1)pdm09like, 

-- A/Croatia/10136RV/2023 (H3N2)-like, 

-- B/Austria/1359417/2021-like (B/Victoria lineage) and, in quadrivalent vaccines, 

-- B/Phuket/3073/2013-like (B/Yamagata lineage) virus antigens. 

Cell culture-propagated and recombinant vaccines contained A/Wisconsin/67/2022 (H1N1)pdm09-like, A/District of Columbia/27/2023 (H3N2)-like and B/Austria/1359417/2021-like (B/Victoria lineage) virus antigens. 

Recent A(H1N1)pdm09 viruses with HA genes from clades 5a.2a (subclade C.1.9.3) and 5a.2a.1 (subclades D.3.1 and D.3.1.1) were analysed in HI assays using these human serum panels. 

When compared to the responses to cell culture-propagated A/Wisconsin/67/2022 (H1N1)pdm09-like vaccine reference viruses, post-vaccination geometric mean titres (GMTs) were significantly reduced for some recently circulating viruses from D.3.1 and D.3.1.1 subclades. 

Of 1 161 A(H1N1)pdm09 virus clinical samples and isolates examined by genetic and/or phenotypic analyses, 15 viruses showed evidence of reduced susceptibility to neuraminidase inhibitors (NAIs): seven had an H275Y neuraminidase (NA) substitution and eight had I223V and S247N substitutions. 

Of 1 331 A(H1N1)pdm09 viruses examined by genetic and/or phenotypic analyses, no viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil. 

Influenza A(H3N2) viruses  

Phylogenetic analysis of the HA gene sequences of A(H3N2) viruses collected since September 2025 showed that the vast majority of viruses belonged to one of the J.2 subclades {6}, expressing HA N122D and K276E substitutions. 

HA genes have diversified with many subclades; J.2.2 (characterized by S124N), J.2.3 (characterized by N158K, K189R and S378N), J.2.4 (characterized by T135K [a potential loss of an N-glycosylation site] and K189R), and K (formerly designated as J.2.4.1; characterized by K2N, S144N [a potential addition of an N-glycosylation site], N158D, I160K, Q173R, T328A and S378N). 

During this reporting period, subclade K viruses were detected in all regions and predominated in many countries. 

There was still circulation of other J.2 subclades, notably J.2 or J.2.3 in South America, J.2.2 or J.2.4 in Africa and Asia.  

Post-infection ferret antisera raised against cell culture-propagated A/District of Columbia/27/2023-like and egg-propagated A/Croatia/10136RV/2023-like (clade 2a.3a.1, subclade J.2) viruses, representing the A(H3N2) component for the NH 2025-2026 influenza vaccines, showed poor recognition with recently circulating subclade J.2.3 (e.g., A/Netherlands/10685/2024), J.2.4 (e.g., A/Sydney/1359/2024) and K (e.g., A/Darwin/1415/2025) viruses. 

Ferret antisera raised against reference viruses from J.2.3 subclades showed good recognition of viruses expressing HA from J.2.3, but poor recognition of other subclades.  

Post-infection ferret antisera raised against cell culture-propagated A/Sydney/1359/2024-like and eggpropagated A/Singapore/GP20238/2024-like J.2.4 viruses, representing SH 2026 influenza vaccines, recognized most J.2.4 viruses and many subclade K viruses well. 

However, subclade K viruses and J.2.4 viruses with HA substitutions F79V, S144N (addition of a potential N-glycosylation site), N158D, I160K, T328A were better recognized by post-infection ferret antisera raised against cell culture-propagated A/Darwin/1415/2025-like and egg-propagated A/Darwin/1454/2025-like (subclade K) viruses. 

Human serology studies were conducted using the serum panels as described above by HI and virus neutralization (VN) assays with recent circulating A(H3N2) viruses with HA genes from subclades J.2, J.2.2, J.2.3, J.2.4, J.2.5 and K. 

When compared to titres against cell-propagated A/District of Columbia/27/2023-like vaccine reference viruses, post-vaccination HI GMTs or VN GMTs against many of the recent viruses in all subclades tested were significantly reduced in many serum panels.  

(...)

Of 4 458 influenza A(H3N2) viruses examined by genetic and/or phenotypic analyses, two viruses showed evidence of reduced susceptibility to NAIs; both had an NA E119V substitution. 

Of 4 828 A(H3N2) viruses examined by genetic and/or phenotypic analyses, nine viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil: three had a PA I38T substitution, three had a PA I38I/T substitution, two had a PA I38I/M substitution and one had a PA E199E/G substitution.  

Influenza B viruses  

Since September 2025, influenza B viruses were detected in all WHO regions, and all those characterized belonged to the B/Victoria lineage. 

There have been no confirmed detections of circulating B/Yamagata lineage viruses after March 2020.  

All HA genes of B/Victoria lineage viruses characterized during this reporting period belonged to clade 3a.2 with HA substitutions A127T, P144L, and K203R. 

Viruses with clade 3a.2 HA genes have diversified further, forming several subclades (C.1-C.5)7. 

Viruses designated as C.5, C.5.1, C.5.6, C.5.6.1 and C.5.7, all of which had the HA substitution D197E, circulated at varying proportions in different regions. 

Viruses designated as C.3 have HA substitutions E128K, A154E and S208P. 

Subclade C.3.1 viruses shared additional mutations D197N (addition of a potential N-glycosylation site) and P208S. 

Recent C.3 viruses which had additional changes D197N (addition of a potential N-glycosylation site), S255P and I267V and C.3.1 viruses have been detected in increasing proportions in Eastern Asia and North America in recent weeks. 

Antigenic analysis showed that post-infection ferret antisera raised against B/Austria/1359417/2021-like viruses (3a.2), representing the vaccine viruses for the SH 2026 and NH 2025-2026 influenza seasons, recognized viruses within the C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades well. 

C.3 and C.3.1 subclade viruses with the HA substitution D197N were recognized poorly. 

Post-infection ferret antisera raised against cell culture-propagated viruses from subclade C.3.1 (e.g., B/Pennsylvania/14/2025) recognized recently circulating viruses from C.3, C.3.1 and other 3a.2 subclades well. 

All available egg isolates for subclade C.3 and C.3.1 viruses acquired substitutions that remove the potential N-glycosylation site at HA 197 to 199. 

Post-infection ferret antisera raised against egg-propagated viruses from subclade C.3.1 (e.g., B/Tokyo/EIS13-175/2025, B/Tokyo/EIS13-011/2025, B/Perth/115/2025) showed reduced recognition of recently circulating viruses from C.3 and C.3.1 subclades compared to that of the cell equivalent.  

(...)

In human serology studies, recently circulating B/Victoria lineage viruses with HA genes from clade 3a.2 subclades C.3, C.3.1, C.5.1, C.5.6, C.5.6.1 and C.5.7 were tested using the serum panels described above. 

When compared to titres against egg- or cell culture-propagated B/Austria/1359417/2021-like vaccine reference virus, titres against most viruses with HA genes from C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades were not significantly reduced; however, titres against viruses with HA genes from C.3 and C.3.1 were significantly reduced in most serum panels. Serology studies were not performed for B/Yamagata lineage viruses.  

Of 549 influenza B/Victoria lineage viruses examined by genetic and/or phenotypic analyses, two showed evidence of reduced or highly reduced susceptibility to NAIs, both with an NA M464T substitution. 

Of 760 B/Victoria lineage viruses examined by genetic and/or phenotypic analyses, no viruses showed evidence of reduced susceptibility to the endonuclease inhibitor baloxavir marboxil.  

Recommended composition of influenza virus vaccines for use in the 2026-2027 northern hemisphere influenza season  

Since September 2025, A(H1N1)pdm09 viruses circulated globally. The majority of viruses had HA genes belonging to the 5a.2a.1 clade which has further diversified into the D.3.1 and D.3.1.1 subclades. 

Postinfection ferret antisera raised against the northern hemisphere (NH) 2025-2026 A(H1N1)pdm09 vaccine viruses (cell culture-propagated A/Wisconsin/67/2022 and egg-propagated A/Victoria/4897/2022) and the southern hemisphere (SH) 2026 A(H1N1)pdm09 vaccine viruses A/Missouri/11/2025 recognized D.3.1 and D.3.1.1 viruses well. 

In human serology studies, post-vaccination geometric mean titres (GMTs) were significantly reduced for some recently circulating A(H1N1)pdm09 viruses when compared to the responses to cell culture-propagated A/Wisconsin/67/2022 A(H1N1)pdm09-like vaccine reference viruses. 

Since September 2025, A(H3N2) viruses circulated and predominated globally. 

The vast majority of A(H3N2) viruses collected had HA genes from subclades of J.2 and have continued to diversify with subclade K (previously designated as J.2.4.1) viruses predominating in most regions. 

Post-infection ferret antisera raised against NH 2025-2026 influenza season vaccine viruses (cell culture-propagated A/District of Columbia/27/2023 and egg-propagated A/Croatia/10136RV/2023) recognized some J.2 viruses well but showed poor recognition of viruses from subclades J.2.3, J.2.4 and K. 

Post-infection ferret antisera raised against subclade K viruses (cell culture-propagated A/Darwin/1415/2025 and egg-propagated A/Darwin/1454/2025) showed improved recognition of K viruses compared to post-infection antisera raised against NH 2025-2026 and SH 2026 A(H3N2) vaccine viruses. 

When compared to titres against cell culture-propagated A/District of Columbia/27/2023-like vaccine reference viruses, human post-vaccination haemagglutinin inhibition (HI) GMTs or virus neutralisation (VN) GMTs against many of the recent viruses in J.2.3, J.2.4 and K subclades were significantly reduced. 

Since September 2025, influenza B virus detections remained low globally, although some countries had increased detections in recent weeks. All circulating influenza B viruses characterized belonged to the B/Victoria lineage, and had HA genes belonging to clade 3a.2 with substitutions A127T, P144L and K203R. 

Post-infection ferret antisera raised against B/Austria/1359417/2021-like viruses (3a.2), representing the vaccine viruses for the SH 2026 and NH 2025-2026 influenza seasons, recognized viruses within the C.5.1, C.5.6, C.5.6.1 and C.5.7 subclades well. C.3 and C.3.1 subclade viruses with HA substitution D197N were recognized poorly. 

Post-infection ferret antisera raised against cell culture-propagated viruses from subclade C.3.1 (e.g., B/Pennsylvania/14/2025) recognized recently circulating viruses from C.3, C.3.1 and other 3a.2 subclades well. All available egg isolates for subclade C.3 and C.3.1 viruses (e.g., B/Tokyo/EIS13-175/2025) acquired egg-adaptive mutations that remove the potential N-glycosylation site at HA 197 to 199, leading to post-infection ferret antisera raised against egg-propagated viruses from subclade C.3.1 (e.g., B/Tokyo/EIS13-175/2025) showing reduced recognition of recently circulating viruses from C.3 and C.3.1 subclades compared to that of the cell equivalent. 

Human serology assays showed that post-vaccination titres against most recent B/Victoria lineage viruses with HA genes from subclades C.5.1, C.5.6, C.5.6.1 and C.5.7 were not significantly reduced when compared to titres against egg- or cell culturepropagated B/Austria/1359417/2021-like vaccine reference viruses. Titres against viruses with HA genes from subclade C.3 and C.3.1 were significantly reduced in most serum panels.  

For vaccines for use in the 2026-2027 northern hemisphere influenza season, WHO recommends the following:  

Egg-based vaccines  

• an A/Missouri/11/2025 (H1N1)pdm09-like virus;  

• an A/Darwin/1454/2025 (H3N2)-like virus; and  

• a B/Tokyo/EIS13-175/2025 (B/Victoria lineage)-like virus.  

Cell culture-, recombinant protein- or nucleic acid-based vaccines  

• an A/Missouri/11/2025 (H1N1)pdm09-like virus;  

• an A/Darwin/1415/2025 (H3N2)-like virus; and  

• a B/Pennsylvania/14/2025 (B/Victoria lineage)-like virus.  

Lists of prototype viruses for egg-, cell culture-, recombinant protein- and nucleic acid-based vaccines together with candidate vaccine viruses (CVVs) suitable for the development and production of human influenza vaccines are available on the WHO website {8}. 

A list of reagents for vaccine standardization, including those for this recommendation, can also be found on the WHO website.  

CVVs and reagents for use in the laboratory standardization of inactivated vaccines may be obtained from:  

• Therapeutic Goods Administration, P.O. Box 100, Woden, ACT, 2606, Australia (email: influenza.reagents@health.gov.au; website: http://www.tga.gov.au).  

• Medicines and Healthcare products Regulatory Agency (MHRA), Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, the United Kingdom of Great Britain and Northern Ireland  • (email: enquiries@mhra.gov.uk; website: http://www.nibsc.org/science_and_research/virology/influenza_resource_.aspx). 

• Division of Biological Standards and Quality Control, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, the United States of America (email: cbershippingrequests@fda.hhs.gov).  

• Research Centre for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan (email: flu-vaccine@nih.go.jp).  

Requests for reference viruses should be addressed to:  

• WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia (email: whoflu@influenzacentre.org; website: http://www.influenzacentre.org).  

• WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Japan Institute for Health Security 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan (email: whocc-flu@nih.go.jp).  

• Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop H17-5, Atlanta, GA 30329, the United States of America (email: InfluenzaVirusSurvei@cdc.gov; website: http://www.cdc.gov/flu/).  

- WHO Collaborating Centre for Reference and Research on Influenza, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, the United Kingdom of Great Britain and Northern Ireland (Tel: +44 203 796 1520 or +44 203 796 2444, email: whocc@crick.ac.uk;  • website: http://www.crick.ac.uk/research/worldwideinfluenza-centre).  

• WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Changping District, 102206, Beijing, China. (tel: +86 10 5890 0851; email: fluchina@ivdc.chinacdc.cn; website: https://ivdc.chinacdc.cn/cnic/en/).  

WHO provides weekly updates {9} of global influenza activity. Other information about influenza surveillance, risk assessment, preparedness and response can be found on the WHO Global Influenza Programme website {10}.  

Acknowledgements  

The WHO recommendation on vaccine composition is based on the year-round work of the WHO Global Influenza Surveillance and Response System (GISRS). We thank the National Influenza Centres (NICs) of GISRS, and non-GISRS laboratories including the World Organization for Animal Health (WOAH) and the Food and Agriculture Organization of the United Nations (FAO) Network of Expertise on Animal Influenza (OFFLU), who contributed information, clinical specimens, viruses and associated data; WHO Collaborating Centres of GISRS for their in-depth characterization and comprehensive analysis of viruses; University of Cambridge for performing antigenic cartography and phylogenetic analysis; WHO Essential Regulatory Laboratories of GISRS for their complementary virus analyses and contributions from a regulatory perspective; and laboratories involved in the production of high growth/yield reassortants as candidate vaccine viruses. We also acknowledge the GISAID Global Data Science Initiative for the EpiFluTM database and other sequence databases which were used to share gene sequences and associated information; modelling groups for virus fitness forecasting; and the Global Influenza Vaccine Effectiveness (GIVE) Collaboration for sharing estimates of influenza vaccine effectiveness on a confidential basis.  

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{1} Recommendations for influenza vaccine composition: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations 

{2} Description of the process of influenza vaccine virus selection and development: http://www.who.int/gb/pip/pdf_files/Fluvaccvirusselection.pdf 

{3} Vaccines in tropics and subtropics: https://www.who.int/teams/global-influenza-programme/vaccines/vaccine-in-tropics-and-subtropics 

{4} Vaccines against influenza WHO position paper – May 2022. Wkly Epidemiol Rec 2022; 97 (19): 185 - 208. Available at: https://iris.who.int/handle/10665/354264 

{5} Real-time tracking of influenza A(H1N1)pdm09 evolution: https://nextstrain.org/seasonal-flu/h1n1pdm/ha/2y?c=subclade 

{6} Real-time tracking of influenza A(H3N2) evolution: https://nextstrain.org/seasonal-flu/h3n2/ha/2y?c=subclade 

{7} Real-time tracking of influenza B/Victoria lineage evolution: https://nextstrain.org/seasonal-flu/vic/ha/2y?c=subclade 

{8} Candidate vaccine viruses: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations/candidate-vaccine-viruses 

{9} Current respiratory virus update: https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/influenza-updates 

{10} Global Influenza Programme: https://www.who.int/teams/global-influenza-programme 

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Source: 

Link: https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2026-2027-northern-hemisphere-influenza-season

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