Evaluation of Cross-Immunogenicity of #Ferret #Antisera Following Immunization with #H5N1 #Vaccine Strains

 

Abstract

Background: 

Highly pathogenic avian influenza H5N1 viruses of clade 2.3.4.4b have spread globally since 2021, causing extensive outbreaks in avian populations and repeated spillovers into diverse mammalian hosts, including humans. These cross-species transmission events highlight ongoing pandemic risks and underscore the need for vaccine strategies that reflect viral evolution at the human–animal interface. Despite the availability of licensed H5 vaccines and newly recommended World Health Organization (WHO) candidate vaccine viruses (CVVs), the extent to which these vaccines elicit cross-reactive antibody responses against contemporary clade 2.3.4.4b viruses, including mammalian spillover isolates of avian origin, remains incompletely characterized. 

Method: 

In this study, ferret antisera were generated using four WHO-recommended H5 CVVs, including a clade 1 strain (A/Vietnam/1194/2004) and three clade 2.3.4.4b strains (A/Astrakhan/3212/2020, A/American wigeon/South Carolina/22-000345-001/2021, and A/Ezo red fox/Hokkaido/1/2022), formulated with alum adjuvant to reflect licensed vaccine formulation used in national preparedness programs. Antibody responses and cross-reactive activity were evaluated using hemagglutination inhibition (HI) and microneutralization (MN) assays against homologous vaccine strains and a feline-origin clade 2.3.4.4b H5N1 field isolate from Korea, A/Feline/Korea/SNU-01/2023. 

Results: 

Antisera induced by clade 2.3.4.4b CVVs showed cross-reactive antibody responses against homologous and heterologous clade 2.3.4.4b viruses and demonstrated measurable HI and MN responses against the feline-origin field isolate. In contrast, antisera raised against the clade 1 Vietnam CVV exhibited limited cross-reactivity against clade 2.3.4.4b viruses. Overall, clade 2.3.4.4b CVVs generally showed higher antibody responses than the clade 1 vaccine strain across multiple panels. 

Conclusions: 

These findings provide descriptive insights into antigenic differences between clade 1 and clade 2.3.4.4b viruses and support the antigenic relevance of clade 2.3.4.4b CVVs for contemporary H5N1 strains. This study highlights the importance of ongoing antigenic evaluation to inform vaccine strain selection within a One Health framework.

Source: 

Link: https://www.mdpi.com/2076-393X/14/4/301

____

A Phase 1/2 Dose-Ranging Safety and Immunogenicity Study of #mRNA-Based Candidate #Pandemic #Influenza #Vaccines in Healthy Adults

 

Abstract

Background

Influenza A viruses pose a persistent pandemic threat. We report safety, reactogenicity, and immunogenicity findings for mRNA-1018 pandemic influenza vaccine candidates from a phase 1/2 study in healthy adults.

Methods

In Part A, participants were randomized to receive 1 of 4 mRNA-1018 candidates at 1 of 3 dose levels across 2 influenza A groups: (1) H5N8/H5-only or (2) H7N9/H7-only. H5N8 and H7N9 candidates were administered at 25, 50, or 100-µg and H5-only and H7-only at 12.5, 25, or 50-µg. Part B participants were randomized to receive 12.5, 25, or 50-µg H5-only-CG. Primary objectives were to evaluate the safety and reactogenicity of vaccine candidates. Secondary objectives included evaluation of humoral immunogenicity through day 205 by hemagglutination inhibition (HAI), neuraminidase inhibition, and microneutralization assays.

Results

Parts A and B comprised 1195 and 304 dosed participants, respectively. Overall, solicited local adverse reactions (ARs) within 7 days of vaccination occurred in 76.8% of participants across vaccine candidates and dose levels, most commonly injection-site pain. Solicited systemic ARs were reported in 62.8% of participants, most frequently fatigue and headache. Solicited ARs were predominantly grade 1–2 in severity, with few grade 3 and no grade 4 events. Post-vaccination immune responses, assessed absolutely, by HAI titers and dynamically, by seroconversion rates, tended to increase with vaccine dose. H5-based candidates induced stronger strain-specific HAI, but with comparable microneutralization titers, versus H7-based candidates.

Conclusions

Vaccine candidates were sufficiently well-tolerated and immunogenic. Further development of mRNA pandemic influenza vaccines is warranted for pandemic preparedness.

Source: 

Link: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciag278/8662346

____

#Prion shedding is reduced by chronic wasting disease {#CWD} #vaccination

 

Abstract

Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30–90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014166

____

#Measles - #Bangladesh (WHO, D.O.N., April 23 '26)

 

Situation at a glance

On 4 April 2026, the National International Health Regulations (IHR) Focal Point for Bangladesh notified WHO of a nationwide increase in measles cases, geographically affecting 58 out of 64 districts across all eight divisions in Bangladesh. 

A total of 19 161 suspected measles cases and 2897 laboratory-confirmed measles cases have been reported between 15 March and 14 April 2026, including 166 measles related deaths (CFR 0.9%). 

The majority (79%) of the reported cases are children aged under 5 years. 

A targeted measles-rubella (MR) vaccination campaign started on 5 April, and various outbreak response measures are ongoing including strengthening nationwide surveillance and epidemiological analysis to enhance case detection and reporting. 

Based on currently available information, WHO assesses the risk at the national level as high due to ongoing transmission across multiple divisions, the large number of susceptible children, documented immunity gaps, and the occurrence of suspected measles-related deaths.

Description of the situation

On 4 April 2026, the National IHR Focal Point of Bangladesh notified WHO of a significant increase in measles cases, driven by sustained domestic transmission. 

Since January 2026, Bangladesh has experienced a marked increase in measles cases. 

Geographically, cases have been reported across all eight divisions, in 58 out of 64 districts (91% of districts), indicating widespread transmission nationally.  

Since 15 March 2026 and as of 14 April, a total of 19 161 suspected measles cases and 2973 laboratory-confirmed measles cases have been reported. 

Moreover, 166 suspected measles-related deaths (CFR 0.9%) and 30 confirmed measles-related deaths (CFR= 1.1%) have been recorded. 

A total of 12 318 hospital admissions and 9772 hospital discharges have also been reported. 

The highest cumulative burden of suspected measles cases since 15 March 2026 has been reported in Dhaka (8263 cases), Rajshahi (3747 cases), Chattogram (2514 cases), and Khulna (1568 cases). 

In Dhaka, cases are concentrated in densely populated informal settlements, including Demra, Jatrabari, Kamrangirchar, Korail, Mirpur, and Tejgaon industrial and slum clusters.  (HEOC, DGHS, 15 April 2026).

Children aged under 5 years account for the majority of reported cases (79%), including children aged under 2 years (66%) and infants aged under 9 months (33%). 

A total of 166 suspected deaths have been reported (CFR 1%), mainly among unvaccinated children aged under 2 years.

Epidemiology

Measles is a highly contagious acute viral disease which affects individuals of all ages and remains one of the leading causes of death among young children globally. The mode of transmission is airborne or via droplets from the nose, mouth, or throat of infected persons.

Initial symptoms, which usually appear 10-14 days (range 7-23 days) after infection, include high fever, usually accompanied by a runny nose, bloodshot eyes, cough and tiny white spots inside the mouth. The rash usually appears 10-14 days after exposure and spreads from the head to the trunk to the lower extremities. A person is infectious from four days before up to four days after the appearance of the rash. There is no specific antiviral treatment for measles, and most people recover within 2-3 weeks.

Measles is usually a mild or moderately severe disease. However, measles can lead to complications such as pneumonia, diarrhoea, secondary ear infection, inflammation of the brain (encephalitis), blindness, and death. Postinfectious encephalitis can occur in about one in every 1000 reported cases. About two or three deaths may occur for every 1000 reported cases.

Vaccination with measles containing vaccine is safe and effective, providing protection against measles and its complications for all eligible populations. WHO recommends two doses of Measles Containing Vaccine (MCV) to be provided through the routine immunization schedule. Strong routine immunization systems are therefore critical foundations for achieving and sustaining high levels of population immunity to vaccine preventable diseases such as measles.

WHO further recommends the conduct of Supplementary Immunization Activities (SIAs) or mass immunization campaigns as an effective strategy for delivering vaccination to children who may have been missed by routine services. In protecting vulnerable populations against measles, mass vaccination campaigns can rapidly improve population immunity by reducing the number of susceptible individuals in the population.

Public health response

A nationwide measles-rubella (MR) vaccination campaign was approved by the National Immunization Technical Advisory Group (NITAG) on 30 March 2026, targeting children aged 6–59 months (with expanded coverage for 6–8 months), and started on 5 April in 30 upazilas (sub-districts) of 18 priority districts. A nationwide campaign commenced on 20 April. 

Vitamin A campaign was held throughout the country on 15 March 2025.  During this outbreak response, Vitamin A supplementation is provided to all suspected and confirmed measles cases as an essential component of standard treatment and case management. 

District Rapid Response Teams (RRTs) have been activated, and vaccine procurement fast-tracked by the Ministry of Health. Other outbreak response actions include strengthening routine immunization to prevent further spread of the outbreak, enhancing hospital preparedness, ensuring availability of vitamin A, strengthening isolation capacity, and reinforcing infection prevention and control measures. 

Strengthening nationwide surveillance and epidemiological analysis, is also ongoing including measures to improve case detection and reporting. Trainings are being conducted at health facilities to improve case detection and reporting, and weekly situation reports produced to support evidence-based decision-making. 

National and divisional guidelines have been issued to guide response activities, including vaccination, clinical management, infection prevention and control, patient care pathways, and procurement. 

WHO risk assessment

Measles is a highly contagious viral disease that affects susceptible individuals of all ages and remains one of the leading causes of death among young children globally. Measles can cause serious illness in at-risk groups, including children under 5 years of age, those who are malnourished especially those with vitamin A deficiency and people with weakened immune systems. Measles complications include hearing loss, diarrhoea, pneumonia and blindness. Severe complications of measles include encephalitis, brain damage, and death. 

The current outbreak in Bangladesh is occurring in the context of suboptimal population immunity. A substantial proportion of cases occurred among children who were either unvaccinated or had received only one dose of measles-containing vaccine. In addition, some children were infected before reaching the age of eligibility for vaccination at 9 months. Most cases (91%) occurred among children aged 1 to 14 years, indicating substantial immunity gaps in this age group. 

Before this outbreak, Bangladesh had made substantial progress towards measles elimination. Reported coverage with the first dose of measles-containing vaccine increased considerably between 2000 (89% - WUENIC) and 2016 (118% - WUENIC), while coverage with the second dose also improved between its nationwide introduction in 2012 (22% - WUENIC) and 2024 (121% - WUENIC). During the same period, confirmed measles incidence declined sharply. However, recent declines in MR1 and MR2 coverage due to nationwide stockout of MR vaccine between 2024-2025, combined with routine immunization gaps and the absence of regular nationwide supplementary measles-rubella campaigns since 2020, have increased the number of susceptible children and contributed to the current outbreak. 

The risk at the national level is assessed as high due to ongoing transmission across multiple divisions, the large number of susceptible children, documented immunity gaps, and the occurrence of suspected measles-related deaths. The concentration of cases among unvaccinated and under-vaccinated children including infants too young to be vaccinated, raises concern for continued uninterrupted transmission and severe disease outcomes. 

Overall, the outbreak suggests a reversal from Bangladesh’s previous progress towards measles elimination and highlights increasing vulnerability to sustained transmission. Continued spread is likely unless urgent measures are implemented to strengthen surveillance, rapidly detect and respond to cases, and close immunity gaps through high-quality vaccination activities. 

There are considerable risks of cross-border spread, facilitated by cross-border population movement, with major urban centres such as Dhaka, Chattogram, Sylhet, and Cox’s Bazar being important international travel and transit hubs increasing the likelihood of national and international spread, particularly among unvaccinated or inadequately vaccinated travelers. 

Measles is endemic across the South-East Asia region. The risk is assessed as high at regional level.

Bangladesh shares extensive land borders with India and Myanmar, and population mobility across these borders may facilitate continued transmission. In Myanmar there is a considerable number of unvaccinated/zero dose children. With ongoing conflict and humanitarian crisis, surveillance and response capacities are limited. India, despite achieving high vaccination coverage, has reported a rise in case count over the past six months. Cities with high incidence such as Jashore and Chapainawabganj (an identified hotspot) share busy land crossings with India, thereby increasing the risk of introduction across the border. Despite Bangladesh’s progress towards measles elimination the current outbreak highlights the vulnerability of the population and underscores the fragility of immunization gains.

The risk at the global level is assessed as moderate due to high levels of population mobility, combined with ongoing widespread measles transmission and immunity gaps.

WHO advice

WHO recommends maintaining sustained homogeneous coverage of at least 95% with the first and second doses of the MCV vaccine in all municipalities and strengthening integrated epidemiological surveillance of measles and rubella to achieve timely detection of all suspected cases in public, private, and social security healthcare facilities.  

WHO recommends strengthening epidemiological surveillance in high-traffic border areas to rapidly detect and respond to highly suspected measles cases. Providing a rapid response to imported measles cases to avoid the re-establishment of endemic transmission through the activation of rapid response teams trained for this purpose and by implementing national rapid response protocols when there are imported cases. Once a rapid response team has been activated, continued coordination between the national, sub-national, and local levels must be ensured, with permanent and fluid communication channels between all levels. During outbreaks, it is recommended to establish adequate hospital case management to avoid nosocomial transmission, with appropriate referral of patients to isolation rooms (for any level of care) and avoiding contact with other patients in waiting rooms and/or other hospital rooms.  

WHO recommends vaccination of at-risk populations (without proof of vaccination or immunity against measles and rubella), such as healthcare workers, persons working in tourism and transportation (hotels, airports, border crossings, mass transportation, and others), and international travelers. Implementing a plan to immunize migrant populations in high-traffic border areas, prioritizing those considered at-risk, including both migrants and residents, in these municipalities increases vaccination coverage to increase population immunity.  

In all settings, consideration should be given to providing susceptible contacts with post-exposure prophylaxis (PEP), including a dose of MCV or normal human immunoglobulin (NHIG) (if available) for those at risk and in whom the vaccine is contraindicated. In well-resourced settings, MCV should be provided to susceptible contacts within 3 days. For contacts for whom vaccination is contraindicated or is not possible within 3 days post-exposure, consideration can be given to providing NHIG up to 6 days post-exposure. Infants, pregnant women, and the immunocompromised should be prioritized.  

WHO recommends maintaining a stock of the MR and/or measles, mumps, rubella (MMR) vaccine, and syringes/supplies for control actions of imported cases. Facilitating access to vaccination services according to the national scheme to those from other countries or people from the same country who perform temporary activities in countries with ongoing outbreaks; displaced populations; indigenous populations, or other vulnerable populations.  

WHO does not recommend any restriction on travel and trade based on the information available on the current outbreak.  

Further information

-- World Health Organization. Measles [Internet]. Geneva: World Health Organization; [cited 2026 Apr 6]. Available from: https://www.who.int/health-topics/measles 

-- World Health Organization. Measles fact sheet [Internet]. Geneva: World Health Organization; 2025 Nov 28 [cited 2026 Apr 6]. Available from: https://www.who.int/news-room/fact-sheets/detail/measles  

-- World Health Organization. Immunization dashboard [Internet]. Geneva: World Health Organization; [cited 2026 Apr 6]. Available from: https://immunizationdata.who.int/  

-- World Health Organization. Measles outbreak guide [Internet]. Geneva: World Health Organization; 2022 Aug 31 [cited 2026 Apr 6]. Available from: https://www.who.int/publications/i/item/9789240052079  

-- Directorate General of Health Services (Bangladesh). Press releases [Internet]. Dhaka; [cited 2026 Apr 6]. Available from: https://dghs.gov.bd/pages/press-releases/  

-- Measles vaccines: WHO position paper – April 2017; https://www.who.int/publications/i/item/who-wer9217-205-227

-- Measles: Vaccine Preventable Diseases Surveillance Standards; https://www.who.int/publications/m/item/vaccine-preventable-diseases-surveillance-standards-measles

__

Citable reference: World Health Organization (23 April 2026). Disease Outbreak News: Measles in Bangladesh. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON598

Source: 

Link: https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON598

____

Heterologous Sequential #mRNA #Vaccination of Indian Rhesus #Macaques Elicits Broad Binding and Neutralizing #Antibody Responses Against Diverse #Henipaviruses

 

Abstract

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks.

Source: 

Link: https://www.mdpi.com/1999-4915/18/5/487

____

Dual-route #H5N1 #vaccination induces systemic and mucosal #immunity in murine and bovine #models

 

Abstract

Highly pathogenic H5N1 avian influenza (clade 2.3.4.4b) has spread widely among dairy cattle herds since early 2024, causing major economic losses. This zoonotic event emphasizes the urgent need for H5 vaccines eliciting strong, durable, cross-reactive immune responses in cows. To address this, we immunized mice and cattle with a centralized consensus H5 vaccine, localizing near the central node of the human H5 phylogenetic tree. The vaccine was delivered using serotype-switched adenoviral vectors in a prime–boost regimen, combined with intramuscular and intranasal coadministration to target systemic and mucosal immunity and elicit strong humoral and cellular immune responses. This approach strategically integrates multiple innovative features: centralized consensus immunogens, mucosal targeting, and vector serotype switching aimed at maximizing immune protection against H5N1 viruses. Our results show that vaccination elicits strong humoral and cellular immunity in both mice and calves. In challenge experiments, vaccinated mice were fully protected against lethal infection with divergent H5N1 strains, including A/bovine/Ohio/B24OSU-439/2024. Vaccine-induced immunity was consistent across species, supporting the translatability of the mouse model findings to cattle. Overall, our findings represent a promising approach for immunizing key livestock, including cattle, against highly pathogenic avian influenza H5N1, mitigating agricultural losses, and reducing the risk of zoonotic transmission.

Source: 

Link: https://www.nature.com/articles/s41541-026-01460-6

____

Cross - #protection against highly pathogenic avian #influenza #H5N1 virus from seasonal influenza #vaccines: a systematic review and meta-analysis of #ferret studies

 

ABSTRACT

The recent surge in spillover events of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b to humans and mammals in North America has raised urgent pandemic concerns. Human H5N1 vaccines are unavailable in most countries. We synthesized data from ferret challenge trials to evaluate whether widely available seasonal influenza vaccines confer cross-protection against lethal H5N1 infection. We systematically searched PubMed, Embase, and Web of Science for ferret studies of lethal H5N1 challenge published up to 5 July 2025 (PROSPERO #CRD42024520346). Random-effects meta-analyses were conducted to compare vaccine efficacy (VE) of seasonal influenza vaccines and H5N1 vaccines against H5N1-related mortality. Seroprotection was defined as a neutralizing antibody titre of ≥1:40. We identified 35 studies (157 trials). Seasonal influenza vaccines without N1 did not confer significant cross-protection (five trials; VE 14.8%, 95% CI –3.6 to 30.0). In contrast, VE was 73% for N1-containing seasonal influenza vaccines (19 trials; 95% CI 54–84) and 77% for H5N1 vaccines overall (133 trials; 95% CI 72–82) (p = 0.52). The VE of N1-containing seasonal influenza vaccines was modestly lower than that of H5N1 vaccines with seroprotection (88%; 66 trials; 95% CI 84–91; p = 0.009), but comparable to H5N1 vaccines that did not achieve seroprotection (63%; 67 trials; 95% CI 52–71; p = 0.29). The VE of seasonal influenza vaccines against H5N1 was robust across sensitivity analyses, with no evidence of publication bias (p = 0.99). Seasonal influenza vaccines significantly reduce H5N1-associated mortality in ferret trials, suggesting the cross-protection potential of currently available vaccines. Human studies are warranted.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2654278

____

#SARS-CoV-2 #vaccination and #infection elicit cross-neutralizing responses against clade 3 and 4 #sarbecoviruses

 

Abstract

Two sarbecoviruses, SARS-CoV-1 and SARS-CoV-2 that engage ACE2 through their receptor-binding domains, have caused major human outbreaks. The pandemic potential of sarbecoviruses has prompted the discovery and classification of bat and other zoonotic sarbecoviruses that are also able to use human ACE2 or ACE2 ortholog receptors for infection. However, the current human immunological landscape reactive to these SARS-CoV-2-related viruses is not well profiled. Using a panel of pseudotyped lentiviruses expressing only spike proteins, we assess serum neutralization activity against clade 3 and 4 (also designated as clade 1c) receptor binding domain classified sarbecoviruses in a cohort who received a primary series of COVID-19 mRNA vaccines as well as individuals before and after infection with BA.5 or XBB.1.5 variants. Detectable neutralizing responses against clade 3 and 4 sarbecoviruses are observed in both vaccinees and convalescents and are comparable in magnitude to titers against SARS-CoV-2 variants. Infection with XBB.1.5 increases neutralization titers against SARS-CoV-2 variants as well as against clade 3 and 4 sarbecoviruses. Collectively, our findings suggest that the current immunologic landscape of vaccination and infection may confer some level of immunity against a variety of clade 3 and 4 sarbecoviruses, which should inform future pandemic response and pan-sarbecovirus countermeasure efforts.

Source: 

Link: https://www.nature.com/articles/s41467-026-71662-y

____

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

 

{Summary}

Influenza A(H3N2) subclade K (J.2.4.1) is a genetic branch of H3N2 with 11 mutations in hemagglutinin compared with the A/H3N2/Croatia/10136RV/2023 (H3N2 CR/23) vaccine strain, of which 8 mutations are on the hemagglutinin head surface (...) (...). As of February 2026, influenza A viruses currently represent approximately 96.3% of circulating influenza strains in the US, with H3N2 accounting for 88.4% of influenza isolates and subclade K comprising 91.5% of H3N2 isolates. The rapid expansion of H3N2 subclade K represents a major public health concern. This study reports antibody responses to H3N2 subclade K and other influenza strains before and after influenza vaccination.

(...)

Source: 

Link: https://jamanetwork.com/journals/jama/article-abstract/2846268

____

#Preclinical evaluation of an #mRNA #vaccine developed from the first #human isolate of #bovine #H5N1

 

Highlights

• SM102 and DB-Y ionizable lipids deliver H5 mRNA vaccine with high efficiency and safety

• Vaccine-induced antibody and T cell response protect mice from H5N1 challenge

• Pre-existing H1 immunity does not diminish H5-specific immunogenicity

• Vaccine fully protects chicken against clade 2.3.4.4b/h H5 virus challenge

Summary

Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.

Source: 

Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00119-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379126001199%3Fshowall%3Dtrue

____

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

____

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

____

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

____

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

____

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

____

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

____

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

____

#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

____

#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

____