Mice immunized with #N1 NA in a single cycle infectious virus or in a recombinant nanoparticle #vaccine are protected against lethal challenge with HPAI #H5N1 influenza

 

Abstract

The recent spillover of highly pathogenic (HP) H5N1 clade 2.3.4.4b into dairy cattle and other mammalian species has been concerning. Vaccine candidates that can be rapidly synthesized and implemented are key countermeasures for protecting the human population against emerging pathogens. Here we examine the use of a pH1N1 virus lacking the genetic material for hemagglutinin (HA), limiting the infection to a single cycle (sciIAV) or Cobalt lipid-porphyrin nanoparticles decorated with neuraminidase (NA) of HPAI H5N1 (N1-CoPoP) as vaccine candidates. C57BL/6 mice that were inoculated intranasally with a single dose of pH1N1 sciIAV did not differ in serum NA antibody compared to uninoculated mice. However, mice that were inoculated intramuscularly with the N1-CoPoP alone or in combination with pH1N1 sciIAV had increased N1 IgG antibodies. Upon lethal challenge with HPAIV H5N1, all mice inoculated with either pH1N1 sciIAV or N1-CoPoP were protected from weight loss, unlike unvaccinated mice with substantial body weight losses that succumb to viral infection between 7 and 10 days post infection (dpi). Both pH1N1 sciIAV and N1-CoPoP immunization minimized viral infection such that only one mouse receiving pH1N1 sciIAV had detectable viral titer in the lungs at 4 dpi. By 6 dpi, no mouse inoculated with pH1N1 sciIAV and/or N1-CoPoP had detectable virus in nasal turbinates, lungs or the brain, unlike the high viral titers found in uninoculated mice. Both pH1N1 sciIAV and N1-CoPoP were protective and should be investigated further as alternative vaccine candidates.

Competing Interest Statement

J.F.L. holds interest in POP Biotechnologies. Other authors declare no competing interests.

Funder Information Declared

American Lung Association, https://ror.org/01p3rh655

Texas Biomedical Research Institute

Douglass Foundation

Source: 

Link:  https://doi.org/10.64898/2026.10.11.758125

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Cross-reactive T-cell responses against #BDBV in #humans after rVSVΔG-ZEBOV-GP #vaccination

 

{Excerpts}

(...)

Our study shows that a single immunisation with the available, licensed EBOV vaccine induces T-cell cross-reactivity against BDBV and to a lesser extent against SUDV. Although it is not known whether these T cells contribute to improved clinical outcomes upon BDBV exposure in humans, preclinical studies show that T-cell responses are required for vaccine-mediated protection in non-human primates: CD4 T cell help to B cells is required for protection against disease caused by EBOV,10 and depletion studies have also shown a protective role of CD8 T cells.11

Our study has limitations. Due to the small sample size and single measured timepoint, dose–response differences and long-term persistence of the cross-reactive T-cell response could not be assessed. This study was performed in healthy adults in Germany, thus representativeness of populations in areas affected by the BDBV outbreak is limited.

Although a correlate of protection against disease caused by BDBV has not been defined, our findings provide first evidence that rVSVΔG-ZEBOV-GP vaccination against EBOV induces BDBV-cross-reactive T-cell responses. In the absence of a BDBV-specific vaccine, these data support the systematic evaluation of the available EBOV vaccine within clinical trials during the current outbreak.

Source: 

Link: https://doi.org/10.1016/S1473-3099(26)00529-3

____

Efficacy, safety, and immunogenicity of a 9-valent vaccine (ExPEC9V) for #prevention of invasive #Escherichia coli disease in older #adults: a phase 3, randomised, placebo-controlled trial (E.mbrace)

 

Summary

Background

Invasive Escherichia coli disease (IED) caused by extraintestinal pathogenic Escherichia coli (ExPEC) can lead to bacteraemia and sepsis. ExPEC9V is a conjugate vaccine targeting nine E coli O-serotypes that account for most E coli bloodstream infections. We aimed to evaluate ExPEC9V for safety, immunogenicity, and prevention of IED caused by ExPEC9V O-serotypes in adults aged 60 years and older.

Methods

In this randomised, double-blind, placebo-controlled, phase 3 study conducted at 332 clinical sites in 20 countries (E.mbrace), we enrolled participants aged 60 years and older in stable health and with a history of urinary tract infection (UTI) within the previous 2 years. Participants were randomly assigned (in blocks of no set size with the use of interactive web response system, stratified by age and presence or absence of risk factors for complicated UTI) 1:1 to receive a single dose of intramuscular ExPEC9V or placebo. Participants, study-site personnel, and investigators remained masked to group allocation throughout the study. The primary endpoint was first IED in blood or sterile sites caused by ExPEC9V O-serotypes in the per-protocol efficacy analysis set (all randomly assigned, vaccinated participants without major protocol deviations); secondary endpoints included immunogenicity assessment in a subset of participants. Safety endpoints included solicited (safety subset), unsolicited (full analysis set), and serious (full analysis set) adverse events. A prespecified futility analysis conducted when at least 40% of the expected 53 IED events had occurred indicated lack of efficacy, leading to early study termination. We present final study results (data up to the date of the futility announcement), when 17 701 of the planned 19 800 participants had been vaccinated. This trial is registered with ClinicalTrials.gov (NCT04899336).

Findings

Participants were enrolled between June 30, 2021, and Feb 13, 2025. Of 18 844 individuals assessed for eligibility, 17 701 were enrolled, randomly assigned, and vaccinated (8858 with ExPEC9V and 8843 with placebo). The per-protocol efficacy included 17 637 participants (8822 for ExPEC9V and 8815 for placebo). There were 24 IED cases (11 in vaccine and 13 in placebo groups) caused by ExPEC9V O-serotypes in blood or sterile sites, yielding a vaccine efficacy of 14·63% (95% CI −106·57 to 65·38), indicating no protective effect. ExPEC9V had an acceptable safety profile, with more frequent low-grade adverse events in the ExPEC9V versus placebo group, balanced serious adverse event distribution among both groups, and no vaccine-related deaths.

Interpretation

In this large phase 3 trial of older adults, ExPEC9V did not demonstrate efficacy in preventing first IED caused by ExPEC9V O-serotypes, despite generating robust and sustained antibody responses. Development of the ExPEC9V vaccine has been discontinued.

Funding

Johnson & Johnson and Sanofi.

Source: 

Link: https://doi.org/10.1016/S1473-3099(26)00469-X

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Zoonotic #influenza #H5 #vaccination in #humans in #EU/EEA - Assessment - 7 October 2026 (ECDC, summary)

 

{Summary}

Zoonotic influenza A(H5) vaccination in humans in the EU/EEA | Assessment

7 October 2026

    Highly pathogenic avian influenza A(H5N1) continues to circulate widely in wild birds and cause outbreaks in poultry and other animals across Europe. 

    Despite extensive circulation, human infections remain rare and no human cases have been confirmed in the EU/EEA to date. 

    Considering this, ECDC assesses the risk from A(H5N1) viruses circulating in Europe as low for the general population and low to moderate for people occupationally or otherwise exposed to infected animals or contaminated environments.  

Key findings

    ° Twenty-seven of 30 EU/EEA countries responded to the survey on influenza A(H5) vaccination in humans – national plans and implementation status in EU/EEA. 

        § Eight countries reported having national A(H5) vaccination recommendations in place, eight were currently developing them, and 11 had no plans at the time of the survey. 

    ° Implementation of the plans remained limited: five countries had started vaccination campaigns (Austria, Finland, Lithuania, the Netherlands and Portugal) and three planned to do so within one year. 

        § Priority groups most commonly included in the cohort to be vaccinated were veterinarians and animal-health staff, culling teams, laboratory staff and workers in farming and the poultry sector.  

    ° Most countries reported that they are monitoring or planning to monitor vaccine uptake; the majority through immunisation registries. 

    ° Reported vaccine uptake in reporting countries was generally low outside laboratory settings, but data were incomplete and not comparable across countries.  

    ° Overall, results were heterogeneous in the EU/EEA due to variation in national recommendations, implementation plans, delivery arrangements and uptake monitoring.  

        § For preparedness purposes, countries would benefit from clearly defined programme objectives and scenario-based triggers, tested delivery pathways, targeted communication and uptake-monitoring plans. 

(...)

Source: 

Link: https://www.ecdc.europa.eu/en/publications-data/zoonotic-influenza-ah5-vaccination-humans-eueea

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Cross-clade #protection against #human #H5N1 isolates by a clade 2.3.4.4b HA #mRNA #vaccine in mice

 

Abstract

The recent spread of clade 2.3.4.4b H5N1 high pathogenicity avian influenza (HPAI) viruses into mammals, despite limited human infections to date, has raised serious public health concerns and highlights the need for rapidly deployable vaccines, such as mRNA-based platforms, to strengthen pandemic preparedness. Here, we evaluated the effectiveness of an mRNA vaccine encoding the HA of NIID-002, a WHO-recommended H5 candidate vaccine virus (CVV) derived from A/Ezo red fox/Hokkaido/1/2022 (clade 2.3.4.4b) against A/Texas/37/2024 (TX37; clade 2.3.4.4b) and A/Cambodia/2311257/2023 (Cam23; clade 2.3.2.1e). The mRNA was formulated with ssPalmO, a low-inflammatory self-degradable ionizable lipid nanoparticle (LNP). BALB/c mice were immunized intramuscularly twice with the mRNA-LNP vaccine containing either 1 μg or 10 μg of H5 HA mRNA. After boosting, strong, dose-dependent serum IgG responses against NIID-002 HA were detected by ELISA. The mice were then challenged with a lethal dose of homologous TX37 or heterologous Cam23. All mice in the 10-μg group survived both challenges, demonstrating robust cross-clade protection. In the 1-μg group, complete protection without significant body weight loss was observed against TX37, whereas partial protection was observed following Cam23 challenge. Viral titers were significantly reduced in multiple tissues of the vaccinated mice compared to the unvaccinated controls. Our findings demonstrate that the NIID-002-HA mRNA vaccine confers protection against homologous and heterologous zoonotic H5N1 strains in a mouse model. This low-inflammatory ssPalmO-LNP platform thus supports safe, rapid vaccine development against emerging H5N1 viruses with pandemic potential.

Source: 

Link: https://doi.org/10.1016/j.vaccine.2026.129215

____

#Maternal #vaccination against #COVID19, #influenza, #pertussis, and #RSV: a scoping review

 

Abstract

Pregnancy and early infancy are periods of heightened vulnerability, with SARS-CoV-2 and influenza infections potentially linked to adverse pregnancy outcomes, including preterm birth and stillbirth. Maternal vaccination provides direct protection to mothers by active immunisation
and to infants by passive immunisation. This scoping review mapped and described published literature on maternal vaccination against COVID-19, influenza, pertussis, and respiratory syncytial virus (RSV). It includes information on the outcome domains studied and if timing of vaccination was examined, with the aim of identifying evidence gaps and supporting decision-makers in choosing priority areas for subsequent systematic review topics. A comprehensive literature search across multiple databases of studies published from January 2000 to October 2025 identified 635 publications (540 publications of primary studies, 95 evidence syntheses). Studies on COVID-19 (260 publications of studies, 45 reviews), influenza (161 publications of studies, 29 reviews), pertussis (113 publications of studies, 20 reviews), and RSV (20 publications of studies, 11 reviews) were analysed. Available evidence on COVID-19, influenza, and pertussis vaccination on efficacy, effectiveness, safety and immunogenicity outcomes is considerable. RSV vaccination evidence is limited. Updated systematic reviews would be helpful to clarify the optimal timing of COVID-19 and influenza vaccination and the effectiveness and safety of the coadministration of influenza and pertussis vaccines.

Source: 

Link: https://www.nature.com/articles/s41541-026-01545-2

____

#Recommendations announced for #influenza #vaccine composition for the 2027 southern hemisphere influenza season (WHO, extract)

 

{Excerpts}

(...)

    From February to August 2026, influenza A(H1N1)pdm09, A(H3N2) and influenza B viruses circulated in varying proportions across all regions of the world, causing disease. 

    Influenza A viruses were the most common in most regions, except Northern and Western Africa, North America and Eastern Asia, where influenza B viruses dominated.

    WHO recommends that vaccines for use in the 2027 southern hemisphere influenza season contain 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.

    As part of the review, experts also looked at influenza viruses circulating in animals, particularly those that have caused infections in humans. These animal or zoonotic influenza viruses remain a significant concern because of their potential to cause pandemics.

(...)

Source: 

Link: https://www.who.int/news/item/25-09-2026-recommendations-announced-for-influenza-vaccine-composition-for-the-2027-southern-hemisphere-influenza-season

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A single-cycle, recombinant VSV #platform #Nipah #vaccine cross-protects against #Hendra virus in nonhuman #primates

 

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic paramyxoviruses that produce severe, often fatal disease in humans and animals. Zoonotic spillover of these henipaviruses from the Pteropid bat natural reservoir occurs near-annually in Southeast Asia and Oceania. Outbreaks of NiV disease frequently exceed case fatality rates of 75%, and person-to-person transmission makes controlling outbreaks in low-resource environments challenging. HeV is less transmissible between humans; however, the overall mortality rate is 57%. Approaches to human vaccine development have largely focused on NiV given the larger case burden, and immunogen selection has centered on display of the NiV attachment (G) or fusion (F) surface glycoproteins. However, experimental vaccines displaying these NiV antigens have failed to uniformly cross-protect against HeV disease in preclinical models. The HeV (G) antigen was shown to cross-protect against both HeV and NiV when delivered in a protein subunit form; however, attempts to utilize mRNA or canarypox vectors failed to achieve equivalent protection. We previously developed and evaluated a single-cycle recombinant vesicular stomatitis virus-vectored vaccine displaying the (G) glycoprotein of Nipah virus strain Bangladesh (NiV-B). This experimental vaccine (G*rVSV∆G-NiV-G) demonstrated ideal characteristics of rapid and durable protection against NiV-B challenge in nonhuman primates. In the present work, we show that the G*rVSV∆G-NiV-G vaccine cross-protects against lethal HeV challenge, with the protective response driven by a balance of both cell-mediated and humoral compartments.

Source: 

Link: https://doi.org/10.1371/journal.ppat.1014646

____

Limited added #benefit of seasonal #influenza #vaccination before #H5 vaccination in mice and #ferrets challenged with #H5N1

 

ABSTRACT

Limited A(H5)-specific vaccine supply is expected early in a potential A(H5N1) pandemic, raising the question of whether licensed seasonal influenza vaccines could enhance protection when administered before A(H5) vaccination. We evaluated this strategy in mouse and ferret models using clade 2.3.4.4b A(H5N1) viruses. Seasonal influenza vaccination induced antibodies to seasonal haemagglutinins but did not induce detectable antibodies against A(H5) and did not consistently enhance A(H5)-directed antibody responses after A(H5) vaccination. In lethal challenge studies, seasonal vaccine priming before A(H5) vaccination was associated with improved outcomes compared with A(H5) vaccination alone in one of three mouse experiments, but this effect was not observed in the other two mouse experiments or in ferrets. These findings suggest that seasonal influenza vaccine priming provides limited added benefit to A(H5) vaccine-mediated protection against A(H5N1) under the conditions tested.

Source: 

Link: https://doi.org/10.1080/22221751.2026.2731495

____

Near real-time data on the #human neutralizing #antibody #landscape to #influenza virus in summer of 2026 shows antigenic advance of #H3N2 subclade K region D mutants and #H1N1 D.3.1.1 Sa mutants

 

Abstract

Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains. Here we provide the third installment in this series of measurements by reporting 47,851 titers representing neutralization of 148 viral strains by 325 human sera collected between April and August of 2026. Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary (https://jbloomlab.github.io/flu-seqneut-2026/summary.html) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.

Competing Interest Statement

JDB consults for Pfizer, GSK, Apriori Bio, and Merck. JDB has received stock options in the Vaccine Company. JDB is an inventor on Fred Hutch licensed patents related to techniques to characterize the antigenic effects of viral variation. SEH is a co-inventor on patents that describe the use of nucleoside-modified mRNA as a vaccine platform. SEH reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. ALG reports contract testing to UW from Abbott, Cepheid, Novavax, Pfizer, Janssen, Assembly Biosciences, Aicuris, Innovative Molecules, and Hologic, research support from Gilead, personal consulting fees from Arisan Therapeutics, outside of the described work. JAE reports support to her institution from GSK, Pfizer, Moderna, and is a consultant for GSK, Pfizer, Merck, Meissa vaccines, Moderna, and Shionogi. ST reports research funding from Pfizer for a separate study.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, R01AI165821, F30AI186284, 75N93021C00015

Howard Hughes Medical Institute, https://ror.org/006w34k90

Source: 

Link: https://doi.org/10.64898/2026.09.15.751855

____

Assessment of immune #response induced by ChAdOx1 nCoV-19, Sputnik V, and BNT162b2 #vaccines during #COVID19 #outbreak in #Mexican population: Gene expression of the #cytokine storm

 

Highlights

    • The molecular immune response triggered by vaccines against COVID-19 was analyzed.

    • The evaluated genes were ACE2, CD79B, TMPRSS2, CTSB, FCGR3A and MB-1.

    • These vaccines induce a protective immune response through various mechanisms.

    • Vaccines regulate the immune response through pro- and anti-inflammatory cytokines.

Abstract

Introduction

COVID-19 vaccines using different technological platforms may induce distinct molecular responses. Characterizing gene-expression patterns after vaccination and in fatal COVID-19 may identify pathways associated with vaccination and severe disease.

Objective

To compare immune-, inflammatory-, and SARS-CoV-2-entry-related gene expression after AstraZeneca, Pfizer, or Sputnik V vaccination and with unvaccinated fatal COVID-19.

Materials and methods

Eighty Mexican adults were included: AstraZeneca (n = 19), Pfizer (n = 20), Sputnik (n = 21), and unvaccinated fatal COVID-19 (n = 20). Expression of 11 genes was measured by qPCR at days 30 (D30) and 60 (D60) after vaccination.

Statistical analysis

Longitudinal differences were analyzed by two-way repeated-measures ANOVA. Comparisons with fatal COVID-19 were exploratory. Benjamini–Hochberg correction controlled false discovery rate at 5%.

Results

No differences among vaccines were detected at D30. At D60, IL-10, IL-2, and CD79A differed among selected vaccine groups. Longitudinally, FCGR3A decreased in AstraZeneca and Sputnik, ACE2 decreased in Pfizer and Sputnik, and TMPRSS2 increased in Sputnik. Fatal COVID-19 showed predominantly higher expression of several genes than vaccinated groups. Notably, IL-2 and ACE2 were consistently higher in fatal COVID-19 than in all vaccinated groups at both time points.

Discussion and conclusions

Post-vaccination transcriptional profiles were dynamic, with selected differences emerging at D60, whereas fatal COVID-19 exhibited a distinct profile characterized predominantly by higher expression of immune-, inflammatory-, and viral-entry-related genes. Consistent IL-2 and ACE2 differences highlight molecular pathways potentially associated with severe disease. The observational design, however, precludes causal attribution to vaccination.

Perspectives

Longitudinal studies with appropriate controls are needed to establish the biological significance of these transcriptional patterns.

Source: 

Link: https://doi.org/10.1016/j.meegid.2026.106025

____

Divergent #antibody-mediated population #immunity to #H5, #H7 and #H9 subtype potential #pandemic #influenza viruses

 

Abstract

Influenza continues to cause significant mortality globally and possesses substantial pandemic potential. Assessing pandemic risk requires a clear understanding of existing population immunity. Leveraging a unique large-scale cohort of human sera, we evaluated total and neutralising antibody-mediated immunity to multiple haemagglutinin (HA) proteins, including those from subtypes with high pandemic potential. Our analysis reveals that population immunity is heterogeneous, with distinct age-dependent differences in responses to H5, H7, and H9 avian influenza subtypes. These shifts align with historical circulation patterns of seasonal H1N1 and H3N2 human viruses. Notably, H7 viruses are primarily neutralised through head domain epitopes, while H5 viruses are targeted mainly via stem epitopes, although in both instances some neutralisation occurred via receptor binding site-adjacent epitopes. Furthermore, H7 responses were dominated by non-glycan-targeted IgG2 antibodies, whereas H5 responses were primarily IgG1-mediated. These findings highlight varying levels of susceptibility to influenza across the population, supporting vaccination approaches informed by exposure history.

Competing Interest Statement

CPT has received lecture fees from Moderna.

Source: 

Link: https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v2

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#Bundibugyo virus gp seroreactivity following recombinant VSV–Zaire Ebola virus gp #vaccination in #outbreak-affected populations of #DRC: a longitudinal cohort study

 

Summary

Background

There are currently no licensed vaccines for disease caused by Bundibugyo virus (BDBV). The recombinant vesicular stomatitis virus–Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP) vaccine has been widely deployed during Ebola virus disease outbreaks caused by Ebola virus (EBOV). Human studies have shown cross-reactive BDBV antibody responses following licensed Ebola virus disease vaccine administration, but the durability and longitudinal kinetics of these responses in populations vaccinated during outbreaks remain unknown. We aimed to evaluate BDBV glycoprotein seroreactivity following rVSVΔG-ZEBOV-GP vaccination in two longitudinal cohorts from regions of the Democratic Republic of the Congo affected by Ebola virus disease outbreaks.

Methods

This longitudinal cohort study was done in Mbandaka, Equateur Province, and Beni, North Kivu Province. Individuals aged 1 year and older who received the rVSVΔG-ZEBOV-GP vaccine under the WHO ring-vaccination protocol were eligible for enrolment. These populations were defined as: people with confirmed Ebola virus disease, contacts of people with Ebola virus disease or contacts-of-contacts, and health-care or front-line workers in areas affected by Ebola virus disease. Participants were enrolled from June 2 to July 3, 2018, in Mbandaka and from Aug 15 to 29, 2018, in Beni. Serum samples were collected from vaccine recipients and antibody reactivity was assessed using a multiplex pan-filovirus immunoassay. Both cohorts were followed up over 5 years, with seven data collection periods in each province. We evaluated longitudinal trends in EBOV and BDBV glycoprotein seroreactivity using a pan-filovirus multiplex immunoassay across follow-up visits.

Findings

We analysed 5849 serum samples from 1081 participants. 715 (66%) of 1081 participants were male and 366 (34%) were female. BDBV glycoprotein seroreactivity differed substantially between study sites. At baseline, 16 (3%) of 482 participants in Mbandaka and 62 (10%) of 599 in Beni were seroreactive to BDBV glycoprotein. In Mbandaka, BDBV glycoprotein antibody reactivity remained stable through to 6 months after initial vaccination before increasing from a mean median fluorescent intensity (MFI) of 1238 (SD 1599) at 2·5 years, with 16 (5%) of 355 seroreactive, to 4845 (5881) at 3·5 years and 116 (35%) of 329 seroreactive (p<0·0001), followed by waning at later visits. In Beni, BDBV glycoprotein antibody reactivity increased rapidly after the initial vaccination, with seroreactivity peaking at 21 days to a mean MFI of 6678 (SD 6997) with 283 (52%) of 541 participants seroreactive and at 6 months to an MFI of 6852 (6560) with 270 (54%) of 501 seroreactive. Although antibody levels decreased after 6 months, EBOV glycoprotein and BDBV glycoprotein antibody reactivity remained above baseline through to 5 years after vaccination.

Interpretation

The differing patterns of BDBV glycoprotein seroreactivity observed between Beni and Mbandaka warrant further investigation into the epidemiological and immunological factors associated with this seroreactivity, including the epidemiological significance of baseline seroreactivity observed before vaccination. To our knowledge, these findings provide the first longitudinal human data describing BDBV glycoprotein seroreactivity following licensed Ebola virus disease vaccination in populations living in regions now affected by the current outbreak of disease caused by BDBV. They add to the growing body of human evidence describing cross-reactive antibody responses following licensed Ebola virus disease vaccination and support rigorous clinical evaluation of rVSVΔG-ZEBOV-GP during the ongoing outbreak while BDBV-specific vaccines continue to be developed.

Funding

The US Food and Drug Administration, the Gates Foundation, and the US Defense Advanced Research Projects Agency.

Source: 

Link: https://doi.org/10.1016/S0140-6736(26)01608-9

____

Nationwide Increase in Reported #Human #Rabies #Exposures: Rabies #PEP Administration (US CDC, HAN, Sept. 10 '26, Summary)

 

Summary

    The Centers for Disease Control and Prevention (CDC) is issuing this Health Alert Network (HAN) Health Advisory in response to recent reports of increases in human exposures to rabid or possibly rabid animals and rabies post-exposure prophylaxis (PEP) administration errors. 

    Since July 2026, multiple United States jurisdictions have reported local increases in human rabies exposures involving known rabies vectors or animals in which rabies is less commonly reported. 

    Several high-profile rabies outbreaks and mass rabies exposure events have highlighted the importance of performing careful rabies risk assessments and following evidence-based recommendations for administering PEP. 

    Health departments can help clinicians who provide rabies vaccination in their jurisdictions stay aware of the importance of rabies risk assessments before administering PEP. 

    Clinicians and healthcare facilities can work to make sure that PEP is administered only when appropriate and that human rabies immune globulin (HRIG) and rabies vaccines are administered according to Advisory Committee on Immunization Practices (ACIP) recommendations.

(...)

Source: 

Link: https://www.cdc.gov/han/php/notices/han00533.html

____

#Ebola disease caused by #Bundibugyo virus - #DRC (WHO, September 10 '26): 6,757 cases and 3,267 deaths so far

 

Situation at a glance

    Since the last Disease Outbreak News was published on 28 August 2026, the Bundibugyo virus outbreak in the Democratic Republic of the Congo has expanded to one additional health zone, Kayna, in North Kivu. 

    This increase brings the total number of affected health zones to 61 across six out of 26 provinces of the country: Bas-Uélé, Haut-Uélé, Ituri, North Kivu, South Kivu, and Tshopo. 

    As of 7 September 2026, the Democratic Republic of the Congo has reported 6757 confirmed cases, including 3267 deaths, resulting in a crude case fatality ratio (CFR) of 48.3%. 

    The transmission dynamics remain variable across affected locations, with evidence of ongoing geographical expansion and sustained increase in cases in some health zones. 

    The continuously high CFR highlights the seriousness of the disease and persistent challenges in timely case detection, access to early and adequate patient care, and effective interruption of transmission. 

    Delayed detection of cases continues to increase the risk of further spread within households, communities, and healthcare settings.

Description of the situation

    Since the publication of the previous Disease Outbreak News on 28 August 2026, additional confirmed cases and deaths of Bundibugyo virus disease (BVD) have been reported only in the Democratic Republic of the Congo.

    As of 7 September 2026, a cumulative total of 6778 confirmed cases has been reported: 6757 in the Democratic Republic of the Congo (including two cases diagnosed in the Democratic Republic of the Congo and subsequently treated in Germany), 20 cases in Uganda and one case in France. 

    Overall, 3269 deaths have been reported, including two in Uganda. 

    As of 7 September, at least 1611 patients have recovered, including 1590 in the Democratic Republic of the Congo, 18 in Uganda, two in Germany and one in France.

    The sustained level of transmission in the Democratic Republic of the Congo continues to pose a risk of cross-border spread. Health screening and surveillance activities remain operational at airports, ports, and official land border crossings; however, travel through informal crossing routes persists and may facilitate virus exportation, importation, and subsequent transmission. In this context, strengthened cross-border coordination, together with ongoing surveillance and preparedness efforts, remains critical to limiting further regional spread and supporting an effective public health response.

(...)

Democratic Republic of the Congo

    Since the previous Disease Outbreak News was published on 28 August 2026, an additional 963 confirmed cases, including 481 confirmed deaths, have been reported in the Democratic Republic of the Congo. 

    While part of this increase may be attributable to strengthened surveillance activities, enhanced laboratory testing, improved diagnostic capacity, and reconciliation of previously unreported data, the continued growth in both cases and deaths also reflects sustained community transmission and significant geographic expansion of the outbreak. 

    As of 7 September, the Democratic Republic of the Congo has reported a total of 6757 confirmed cases, including 3267 deaths (CFR 48.3%). 

    A total of 1590 patients have recovered to date.

    Confirmed cases have been reported from 61 health zones (HZ) across six provinces, with 51 HZ from five provinces reporting at least one case in the last 21 days. 

    Ituri remains the most affected province, with 28 of its 36 health zones reporting cases, followed by North Kivu (16/34), Tshopo (7/23), Haut-Uélé (6/13), Bas-Uélé (3/11), and South Kivu (1/34). 

    No new cases have been reported from South Kivu province since 29 May 2026. 

    Kayna HZ in North Kivu province is the most recently affected area. 

    As of 7 September, 71 new confirmed cases had been reported in the preceding 24 hours from 17 health zones located in Ituri, North Kivu, and Haut-Uélé provinces.

    Ituri continues to be the epicentre of the outbreak, accounting for 5406 confirmed cases since the start of the outbreak, including 1114 new confirmed cases reported in the previous 21 days, as of 7 September. 

    North Kivu is the second most affected province, with a cumulative number of 1066 confirmed cases, including 453 reported in the last 21 days, as of 7 September. 

    One of the highest CFR (65.4%) observed in this outbreak has been reported from North Kivu province; and investigations are ongoing to better understand the factors contributing to this elevated mortality rate.

    The number of individuals requiring follow-up as contact has also risen considerably with the expansion of the outbreak. 

    As of 7 September, 85.3% of identified contacts were successfully monitored during the previous 24 hours with 21 359 contacts seen out of 24 719 requiring follow up. 

    The large volume of contacts under surveillance highlights the extent of potential exposure within affected communities and the substantial demands placed on response operations.

    The outbreak continues to unfold within a complex humanitarian setting characterized by insecurity, armed conflict, and widespread population displacement. 

    More than 26 million people are experiencing acute food insecurity, while approximately one million internally displaced persons reside in Ituri Province alone. 

    Ongoing insecurity and displacement limit access to healthcare and essential services, constrain the ability of response teams to reach affected areas, and impede surveillance, case investigation and contact tracing activities. 

    Overcrowding, limited water, sanitation and hygiene services, and restricted access to healthcare in mining communities, informal settlements and sites for internally displaced persons further undermine early case detection, infection prevention and control measures, and the provision of timely care. These conditions also reduce the effectiveness of response interventions and outreach efforts.

Figure 2: Number of confirmed Bundibugyo virus disease cases in the Democratic Republic of the Congo, by date of notification, as of 7 September 2026

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Figure 3: Number of deaths among confirmed Bundibugyo virus disease cases in the Democratic Republic of the Congo by date of notification, as of 7 September 2026. 

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WHO advice

    Based on the currently available information, WHO advises against any restriction of travel to, or trade with, affected countries. 

    WHO continues to closely monitor and, where necessary, verify travel and trade measures in relation to this event.

    The updated Temporary Recommendations issued to States Parties on 24 August 2026 underscore the importance of coordinated outbreak control, strengthened cross‑border collaboration, and sustained surveillance and preparedness to prevent further regional spread and ensure an effective public health response. 

    Rapid recognition of cases, testing and optimized supportive care can reduce mortality, and improve community perceptions and acceptance of health care within the response.

    On 7 August, the WHO Technical Advisory Group on candidate vaccine prioritization released a report regarding possible candidate vaccines for Bundibugyo virus disease. 

    The members recommended that Ervebo, the only licensed Ebola vaccine (previously known as ebolavirus Zaire), be prioritized for inclusion in a randomized clinical trial in the context of the ongoing outbreak in the Democratic Republic of the Congo. 

    Following a review of additional evidence on 19 August 2026, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) concluded that available evidence remains insufficient to support the programmatic use of Ervebo for the prevention of BVD, and that its efficacy against BVD in humans remains unknown. 

    WHO therefore recommends that Ervebo be used for BVD only within the context of a research protocol.  

    Ervebo vaccination of healthcare and frontline workers is now underway. As of 6 September 2026, a total of 2007 people had been vaccinated across six health zones in three provinces: Tshopo, Bas-Uélé and Ituri.

    On 2 July, a clinical trial to find effective treatments against BVD began patient enrollment on 2 July. The trial, known as the PARTNERS trial, is now open in five different clinical management facilities in Ituri province, and has enrolled over 300 people who are confirmed cases.  

(...)

Source: 

Link: https://www/who.int/emergencies/disease-outbreak.news.item/2026-DON617

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Pan - #Ebolavirus nanoparticle #vaccine provides protection in rodents from lethal #infection by #Zaire and #Sudan viruses

 

Abstract

Both Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) are members of the genus Ebolavirus and cause outbreaks marked by high fatality rates and repeated spillover from animal reservoirs. Filoviral glycoproteins (GPs) are the primary targets of neutralizing antibodies and form the basis of current vaccines. Here we describe the design, structural characterization, and evaluation of two-component self-assembling icosahedral I53-50 nanoparticles displaying prefusion EBOV or SUDV GP antigens, either individually or in cocktail and mosaic multivalent formats. EBOV-GP-I53-50 and SUDV-GP-I53-50 nanoparticles elicited strong homologous protection in mice and guinea pigs. In the mouse-adapted EBOV model (maEBOV), mosaic and cocktail formulations produced weak survival below that of the matched EBOV-GP-I53-50 GP immunogen. In contrast, in the gpaSUDV guinea pig model (gpSUDV), cocktail and mosaic nanoparticles elicited robust protection against gpSUDV, and detectable antibody responses to both SUDV and EBOV GPs. These findings demonstrate that multivalent GP-I53-50 nanoparticle immunogens can protect rodents from death, severe clinical signs of disease, and weight loss in relevant models. Together with the established clinical safety of the I53-50 platform, these results support continued efforts toward the development of a pan-ebolavirus vaccine.

Source: 

Link: https://www.nature.com/articles/s41467-026-76114-1

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Elicitation of Potent #H5N1 - and #H7N9-Neutralizing #Antibody Responses in Rh. Macaques by Sequential Heterologous #Vaccination with #mRNA and Adenoviral Vectors Encoding Full-Length Hemagglutinins

 

Abstract

Highly pathogenic avian influenza (HPAI) represents an enormous pandemic risk amid the ongoing H5N1 panzootic. HPAI, defined by its high lethality in domestic poultry, includes the influenza A virus (IAV) H5N1 and H7N9 subtypes and has a 40–50% case fatality rate in humans. To facilitate the development of efficacious HPAI vaccination regimens and isolation of HPAI-neutralizing monoclonal antibodies (nmAbs) for prophylactic and therapeutic use, we performed a proof-of-concept pilot study wherein we developed an array of mRNA and adenovirus-vectored vaccines encoding HPAI hemagglutinins (HAs) and then assessed their immunogenicity in IAV-naïve Indian rhesus macaques (RMs). All RMs developed binding IgG recognizing both HPAI HAs. HPAI-nAbs were detected in RMs vaccinated with full-length HAs, but not in RMs vaccinated with HA stems alone. Potent HPAI neutralization activity was observed in two animals with serum ID50 titers of ~1:100,000 against H5N1 and ~1:50,000 against H7N9. Most RMs developed cross-reactive IgG recognizing the HAs of additional IAV subtypes, and HA-specific B cells were readily identifiable in vaccinee PBMCs by flow cytometric analysis. The results of our pilot study suggest that elicitation of potent HPAI-nAb responses is enhanced by vaccination with the HA head domain and that vaccination with the HA stem alone tends to elicit binding non-nAbs. Furthermore, use of our fluorophore-conjugated HA probes to identify HA-specific B cells could enable HPAI-nmAb isolation. Collectively, our findings could facilitate the development of novel vaccines and nmAb therapeutics leveraging the superior neutralization potency of HA head-specific Abs to prevent and treat HPAI infections in humans.

Source: 

Link: https://www.mdpi.com/1999-4915/18/9/981

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#Safety, humoral and cellular immune responses to a pre-pandemic adjuvanted #influenza #H5N8 #vaccine

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008583?via%3Dihub

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Sex differences in #vaccine-induced #neuraminidase cross-recognition impact #H5N1 #dissemination to the lower respiratory tract in mice

 

Abstract

H5N1 vaccines have been poorly immunogenic in humans, creating a challenge for vaccine development. Seasonal influenza vaccines offer some cross-protection against H5N1, but there has been no consideration of whether protection differs between the sexes. We investigated sex differences in antibody responses following receipt of either beta-propiolactone inactivated whole virus H1N1 or H5N1 (LAIV backbone) vaccines in C57BL/6 mice. Using systems serology assays, vaccination induced strong homologous and heterologous antibody responses, with females generating greater IgG titers than males against whole virus H1N1 and H5N1, which was primarily mediated by greater IgG responses to neuraminidase (NA) than hemagglutinin (HA) protein. Cross-reactive H5N1 IgG titers were greater among H1N1-vaccinated females, and primarily mediated by greater N1-specific IgG titers. IgG2b and IgG2c were the primary antibody isotypes generated in response to these vaccines, with females having greater IgG2b titers and enhanced binding to FcγRIV for avian and human NA than males following either homologous or heterologous vaccination. Antibody-dependent complement deposition was measured as an FcR-mediated non-neutralizing response against HA and NA and was more robust among H1N1 and H5N1 vaccinated females than their male counterparts in response to homologous HA only. Vaccinated females tended to have greater neutralizing antibody titers than males against the homologous vaccine strain, with limited cross-neutralizing antibodies detected in either sexes. Neuraminidase inhibition titers were greater in vaccinated females than males against the heterologous virus following H1N1 vaccination and against both the vaccine and heterologous viruses following H5N1 vaccination. When H1N1 and H5N1 vaccinated mice were challenged with a lethal dose of A/Texas/37/2024 H5N1, all H5N1 vaccinated mice were protected, regardless of sex. Among H1N1 vaccinated mice, while both sexes were protected against disease, H1N1 vaccinated females restricted virus to the upper respiratory tract and had lower pulmonary virus titers than males at 3 days post challenge. These findings highlight that sex differences in vaccine-induced NA-specific antibody responses are associated with differential respiratory dissemination of H5N1 and that sex should be considered in studies of vaccine-induced cross-reactive influenza immunity.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIH/NIAID Johns Hopkins Center of Excellence for Influenza Research and Response, 75N93021C00045

Richard Eliasberg Family Foundation

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.26.728011v3

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Experimental #reproduction numbers disentangle #vaccine effects on susceptibility and infectiousness during #H5N1 #transmission in #geese

 

Abstract

Vaccination against high pathogenicity avian influenza virus (HPAIV) is increasingly used to protect poultry, but vaccine performance is commonly inferred from clinical protection and virus shedding rather than measured transmission. We asked whether reproduction numbers from controlled transmission experiments can quantify how vaccination changes susceptibility and infectiousness. Domestic geese were prime-boost vaccinated with an H5 clade 2.3.4.4b RNA-replicon vaccine and challenged with homologous HPAIV H5N1. Replicated seeder-sentinel groups represented transmission among unvaccinated animals, to vaccinated contacts, and from vaccinated breakthrough-infected animals. Vaccinated directly challenged geese remained clinically protected although all became RT-qPCR-positive. Estimated reproduction numbers were R0=4.7 (95% CI, 2.8-8.0) among unvaccinated geese, Rs=2.6 (1.6-4.5) for transmission to vaccinated contacts, Ri=3.7 (2.0-6.8) for transmission from vaccinated infected geese, and Rvacc=2.0 (0.8-4.9) for a fully vaccinated population. Vaccination reduced transmission but did not reduce the point estimate for Rvacc below one under these intensive exposure conditions. Vaccinated infected geese also shed substantially less viral RNA, whereas the estimated reduction in infectiousness was more modest, indicating that RNA shedding alone may not reliably predict transmission reduction. Experimental reproduction numbers therefore provide a direct population-level complement to conventional vaccine endpoints and separate effects on susceptibility from effects on onward transmission.

Competing Interest Statement

Christophe Cazaban is an employee of CEVA Santé Animale, which provided the experimental vaccine used in this study. The remaining authors declare no competing interests.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.02.748824v1

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