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

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#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.  

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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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Immunogenicity and #safety of seasonal #influenza #vaccine co-administered with other vaccines: a systematic review and meta-analysis

 

Abstract

Seasonal influenza remains a leading cause of global morbidity and mortality, highlighting the need for vaccination strategies that improve coverage and streamline vaccine delivery. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs), cohort, case-control, and cross-sectional studies, evaluating immunogenicity and safety of same-day co-administration of influenza vaccines with COVID-19 or other vaccines, compared with non-concomitant administration. Comparators included sequential administration, single vaccine administration or placebo-controlled delayed vaccination. Risk of bias was evaluated using the Cochrane Risk-of-Bias tool for Randomized Trials and Risk of Bias In Non-randomized Studies of Interventions; certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Immunogenicity was assessed using geometric mean fold rise (GMFR) in antibody titres and seroprotection rate. Safety was assessed by adverse event (AE) incidence. 52 eligible studies were included. Influenza immunogenicity was comparable between the co-administration and non-concomitant comparator group across all strains (H1N1 GMFR ratio of means (ROM): 1.02 [95% CI: 0.95–1.10]; H3N2, 1.05 [95% CI: 0.97–1.13]; B strain, 1.01 [95% CI: 0.97–1.05]). Pooled risk ratio (RR) for seroprotection was 1.00 for all three strains with 95% CIs ranging from 0.99–1.01. GMFR for COVID-19 vaccines was modestly reduced under co-administration (ROM 0.84 [95% CI: 0.74–0.95]; p = 0.006). Serious AEs were more frequent in the co-administration group compared to the non-concomitant group (RR 1.41 [95% CI: 1.07–1.86]; p = 0.014; absolute risk difference: 1.56 percentage points). Overall, co-administration preserves influenza immunogenicity but modestly reduces COVID-19 vaccine GMFR. Although safety findings warrant cautious interpretation, the low absolute risk difference supports its feasibility as a strategy to streamline vaccination schedules and improve uptake.

Source: 

Link: https://www.nature.com/articles/s41541-026-01548-z

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#Ring and #community #vaccination for #Bundibugyo virus #outbreak response: a stochastic network modelling study

 

Summary

Background

Vaccination with rVSV-ZEBOV is highly effective against Ebola virus, but protection against Bundibugyo virus (BDBV) is unproven. We evaluated the relative population impact and dose efficiency of a partially cross-protective hypothetical vaccine under operationally realistic constraints during a BDBV outbreak.

Methods

We developed a stochastic transmission model on a clustered household–community contact network with empirically realistic local structure, calibrated to 2026 DR Congo BDBV outbreak data. Time-varying effective reproduction numbers were estimated using a Bayesian renewal model. We evaluated case detection, isolation, contact tracing, reactive ring vaccination (Ring 1: direct contacts of the index case; Ring 2: contacts of contacts), and community vaccination (20–80% coverage). Base-case vaccine effectiveness was 45% and included post-exposure protection against disease and mortality. Primary outcomes were mortality and incidence reductions, total doses, and dose efficiency (doses per death averted) over 90 days, evaluated in a probabilistic sensitivity analysis with 10 000 matched stochastic replicates per strategy.

Findings

Compared with base operations alone (30% detection, 30% tracing), enhanced operations alone (70% detection, 80% tracing) reduced expected mortality by 81·6% (95% uncertainty interval 73·1–87·7). Reactive Ring 2 vaccination under base operations reduced mortality by 24·6% (18·0–29·6), requiring 35·1 doses per death averted. Added to enhanced operations, Ring 2 vaccination reduced mortality by 83·6% overall (76·4–89·0), an incremental benefit of 10·5% (6·2–15·6) beyond enhanced operations alone. Community vaccination at 20%, 40%, 60%, and 80% coverage reduced mortality by 44·7% (34·8–52·5), 67·4% (56·2–74·3), 79·8% (70·4–85·3), and 86·6% (79·2–90·4), respectively, requiring 53·8–111·4 doses per death averted.

Interpretation

Strengthened case finding, contact tracing, and isolation averted most deaths even without vaccination. Once these operations were strong, reactive ring vaccination added a modest further benefit, whereas rapid community vaccination produced the largest reductions in simulated scenarios but required substantially more doses. A partially protective BDBV vaccine's population-level value will depend principally on rapid, broad delivery.

Funding

Canadian Institutes of Health Research.

Translation

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

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00464-0/fulltext

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#WHO emergency #guidance on use of licensed #Ebola {Zaire} #vaccine during #Bundibugyo virus disease #outbreaks - Interim guidance 31 August 2026 (Summary)

 

Context

    Ervebo® is currently the only licensed Ebola vaccine available. Ervebo®  (rVSV-EBOV-GP) is a live, recombinant vesicular stomatitis virus (rVSV)-based vaccine licensed that was prequalified by the World Health Organization (WHO) in 2019 for the prevention of Ebola virus disease caused by Ebola virus (EBOV, species Orthoebolavirus zairense, previously known as Zaire ebolavirus) in individuals aged one year or older. It is not licensed for use against Bundibugyo virus (BDBV) and therefore the use of Ervebo® against BDBV constitutes off-label use{1} BDBV and EBOV cause Ebola disease that is  clinically similar but are genetically and antigenically distinct virus species. Their  glycoproteins share approximately only 60–65% amino acid sequence  identity, a distinction that is particularly relevant for vaccination because currently  available Ebola vaccines, including Ervebo®, target the viral  glycoprotein.

    Consequently, although Ervebo® is highly effective against EBOV, the  extent to which Ervebo®-induced immunity provides clinically meaningful  protection against BDBV remains unknown. (1)

    On 19 August 2026 (2), the Strategic Advisory Group of Experts on Immunization (SAGE) reviewed and deliberated on the additional evidence that  had become available following the publication of the WHO emergency guidance  on the use of licensed Ebola virus vaccine during Bundibugyo virus disease  outbreaks, 28 May 2026. (3)

    The BDBV outbreak in the Democratic Republic of the Congo has spread  substantially, with continued transmission and high mortality, creating an urgent  need to strengthen outbreak response and reduce preventable deaths. (4) The  severity of the disease and evolving epidemiological situation increases the  imperative to consider all potentially beneficial interventions, while at the same  time carefully weighing the unknown efficacy of Ervebo® against BDBV, and resultant risks.

    A ring vaccination randomized controlled trial (henceforth referred to as  ring RCT) of Ervebo® and BDBV-specific vaccine candidates is planned to be  conducted in the Democratic Republic of the Congo as a matter of urgency. (5) If  well designed and rigorously implemented, the trial would provide the critical  evidence currently lacking on the efficacy of Ervebo® against BDBV.

Assessment of additional evidence on Ervebo® performance against BDBV since May 2026

    Findings from an increased, albeit still limited, number of studies  conducted to date in nonhuman primates and ferrets suggest some  protection by Ervebo® against BDBV-related mortality, while showing little or no  protection against viraemia and clinical disease (...).

    In the absence of an established correlate or surrogate of  protection  against BDBV, the extent to which findings from animal challenge  models (disease and laboratory-based immunological studies) can predict  protection in humans remains unknown. 

    Available human immunogenicity data regarding potential cross-protection  conferred by Ervebo® against BDBV showed that Ervebo® induces cross-reactive BDBV glycoproteinbinding antibodies which are at levels  approximately 5-fold lower than against EBOV, and that cross-neutralization of  BDBV pseudoviruses with neutralizing titres are approximately 3.5–4-fold lower  than against EBOV (...).

    No Ervebo® vaccine efficacy data against BDBV in humans have been  generated yet. 

    There are a small number of anecdotal reports of previously vaccinated  health care workers who subsequently developed BDBV disease and survived.  However, no conclusions regarding vaccine efficacy or effectiveness can be drawn  from these observations because of the very small sample size, the absence of an  appropriate comparator group, the potential for substantial bias, non-systematic  data collection, and the resulting considerable statistical uncertainty.

    Overall, the limited data and anecdotal reports are suggestive of some  protection against BDBV-related mortality and are consistent in trending towards  some as yet unquantified benefit.

    In conclusion, the available data remain insufficient to determine whether Ervebo® provides any clinically meaningful protection against  BDBV in humans or to reliably estimate the magnitude of such protection,  including protection against infection, disease, severe disease or death.

Benefit–risk considerations regarding off-label use of Ervebo® in the context of unknown efficacy against BDBV

    There is currently clinical equipoise regarding the efficacy of Ervebo®  against    BDBV. 

    Vaccine efficacy in humans remains to be established and could range  from high efficacy, with substantial clinical and public health benefit, through  moderate or partial efficacy, to limited or negligible efficacy, with little or no  meaningful protection. The lower limit of the range of potential effects may even  include harm. The potential ratio of benefits and risks of broader use therefore  differ considerably depending on where within this range the true efficacy ultimately lies.

    If efficacy is high or clinically meaningful, broader use while the ring RCT  is underway could potentially reduce severe disease and deaths and, if the vaccine  also protects against infection and transmission, contribute to outbreak  control. In a context where other medical countermeasures remain limited, earlier  access could provide populations at high risk with a vaccine that has a  well-characterized safety profile, while BDBV-specific vaccines remain under  evaluation and are not yet available for use. Use within appropriately designed  research frameworks could also generate complementary real-world effectiveness  data. In addition, vaccinated individuals would be expected to benefit from  protection against Ebola virus disease should they subsequently be exposed during a future EBOV outbreak.

    Conversely, if efficacy is low, negligible or absent, the balance of benefits  and risks would be substantially less favourable. Considerable financial, logistic  and human resources would be diverted to an intervention providing little or no  clinical or public health benefit. These resources could otherwise support  outbreak-control measures of established effectiveness, including surveillance,  contact tracing, timely testing and case detection, isolation, infection prevention  and control, and safe and dignified burials. These resources could also have been better invested in the development of BDBV-specific vaccines.

    A scenario in which Ervebo® provides meaningful protection against  severe disease or death, but limited or no protection against infection, viraemia or  onward transmission, would require careful consideration. Protection against  severe disease or death would constitute an important individual and public health  benefit, even in the absence of substantial effects on infection or  transmission. However, vaccination could then reduce morbidity and mortality without necessarily interrupting transmission. If this efficacy profile is  not clearly understood and communicated, vaccination could lead to false  reassurance among vaccinated individuals, communities and responders,  potentially reducing adherence to established outbreak-control measures. Such  behavioural changes could offset some of the benefits of vaccination and, if  infection and onward transmission are not sufficiently reduced, could contribute to continued transmission and potentially prolong or exacerbate the outbreak.

    If efficacy proves limited or negligible, substantial numbers of  breakthrough cases or deaths could also undermine public trust in the outbreak  response and confidence in Ebola vaccines, vaccination programmes generally,  and the health sector more broadly. Once broader vaccination has commenced, a  subsequent decision to restrict or discontinue Ervebo® use, if the evidence shows  limited efficacy, could itself create important communication and trust challenges.

    There are also important evidence-generation trade-offs. The use of  Ervebo® outside rigorous research protocols could interfere with the feasibility,  recruitment, implementation and scientific integrity of studies, particularly the ring  RCT, designed to establish vaccine efficacy for Ervebo® and BDBV-specific  vaccine candidates (which are expected to have the potential for better  performance against BDBV). This could delay the generation of the robust evidence needed to guide policy. Observational Ervebo® effectiveness  studies could provide useful complementary information but are inherently more  susceptible to bias and confounding than RCTs and may therefore be more difficult  to interpret or insufficiently robust to resolve the central question of  efficacy. Vaccine effectiveness (VE) studies of vaccines with modest efficacy are  particularly prone to these limitations. Hence the value of any observational study  depends partly on the extent to which its design can ensure that uptake of the  intervention is as close to random as possible and that outcome data are collected  systematically from all participants allowing comparable analysis, thereby reducing selection and information biases. Conversely, if the ring RCT  demonstrates clinically meaningful efficacy of Ervebo® and/or BDBV-specific  vaccine candidates, such a trial would provide a strong basis for rapidly updating  policy and expanding vaccine(s) use to benefit the wider population.

    Extensive reliance on Ervebo® could potentially affect community willingness to participate in future studies or receive BDBV-specific vaccines,  which become especially important if the efficacy of Ervebo® against BDBV is insufficient.

    Finally, widespread deployment would have implications for global vaccine security. Largescale use of available Ervebo® doses against BDBV could  temporarily deplete the International Coordinating Group on Vaccine  Provision stockpile and potentially compromise timely access to vaccine for  response to a future outbreak caused by EBOV, against which Ervebo® has demonstrated efficacy and is licensed.

    Taken together, the uncertainties described above reinforce the importance of obtaining robust efficacy data as rapidly as possible while  carefully weighing the potential benefit of any broader use against its potential negative consequences.

(...)

{1} Use of a vaccine for an unapproved indication (not described in the approved  labelling) or in an unapproved age group, dosage, or route of administration. 

(...)

© World Health Organization 2026. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO licence.

Suggested citation. WHO emergency guidance on the use of licensed Ebola vaccine during Bundibugyo virus disease outbreaks, 31 August 2026. Geneva:  World Health Organization; 2026. https://doi.org/10.2471/B09884

Source: 

Link: https://doi.org/10.2471/B09884

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Immunogen selection and prior #immunity shape #antibody breadth following immunisation with avian #H5 #hemagglutinin

 

Abstract

Avian influenza A viruses pose a persistent zoonotic threat to humans owing to their expanding host range and high case fatality rates. In particular, viruses from the 2.3.4.4b clade of the H5 subtype have now been detected in over 60 mammalian species, raising serious pandemic concerns. Understanding immune recognition of the H5 hemagglutinin (HA) is therefore critical for effective vaccine design and pandemic preparedness. To understand the breadth of cross-recognition induced by different H5 strains, we selected genetically diverse H5 human isolates from 2003-2023 and assessed neutralising antibody responses elicited by adjuvanted recombinant HA protein-based vaccines in C57BL/6 mice. Neutralisation activity of sera was determined against seven H5 HA variants using pseudotyped viruses and a PR8-reassortant virus in micro-neutralisation assays. Our results showed a wide variety of cross-strain neutralisation across H5 HA antigen variants. The conventional vaccine strain A/Indonesia/05/2005 displayed narrow activity against emerging clade 2.3.4.4b viruses, whereas ancestral variants exhibited cross-neutralisation profiles showing a diversity of breath but with limited potency. Polyvalent H5 HA formulations and nanoparticle-displayed H5 HA platforms substantially broadened cross-neutralisation against diverse H5 strains. To examine the impact of pre-existing immunity on H5 vaccine immunogenicity in mouse models, mice were primed with either seasonal influenza infection or quadrivalent influenza vaccine (QIV) prior to H5 HA immunisation. QIV pre-vaccination, but not prior influenza infection, enhanced subsequent neutralizing responses towards A/Fujian-Sanyuan/21099/2017 (clade 2.3.4.4b) H5. Collectively, our results demonstrate that immunogen selection and prior immunity shape antibody breadth following immunisation with avian A(H5) hemagglutinin.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.01.748495v1

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#Bundibugyo virus #glycoprotein seroreactivity following recombinant VSV–Zaire #Ebola virus glycoprotein #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://www.sciencedirect.com/science/article/pii/S0140673626016089?dgcid=rss_sd_all

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Transcriptomic and proteomic signatures following #AS03-adjuvanted #Influenza #H7N9 #vaccine

 

Abstract

Introduction: 

Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood.

Methods: 

We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal influenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that.

Results: 

AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood.

Discussion: 

Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness.

Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Source: 

Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1786231/full

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#WHO and #Africa CDC welcome the allocation of #Ebola #vaccines to the #DRC (WHO, August 20 '26)

 

    Last week, the government of the Democratic Republic of the Congo (DRC) requested a release of Ervebo vaccines from the global Ebola virus disease vaccine stockpile, managed by the International Coordinating Group on Vaccine Provision (ICG). 

    The request was for use of the vaccine in the current Bundibugyo virus disease outbreak. 

    Ervebo vaccine is licensed and recommended for use in outbreaks of Ebola virus disease (previously called Zaire ebolavirus). 

    On Monday, the ICG informed the DRC government of an immediate initial release of 70 000 doses.

    The allocation includes 20 000 doses for a Phase 3 clinical trial to understand the impact of the vaccine on the Bundibugyo virus, and 50 000 doses for frontline and health workers in line with the current recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE).

    It is not known whether Ervebo may be protective against the Bundibugyo virus in humans. 

    Early laboratory and animal data suggest it may provide some protection. Thus, the clinical trial is expected to provide important new evidence, which is essential for policy-makers to inform future use of the Ervebo vaccine. It is key that the people offered the vaccine, in the trial and otherwise, receive information of the risks, potential benefits and limitations related to the use of the vaccine in an outbreak of Bundibugyo virus and are able to provide informed consent. 

    The ICG partners are WHO, the International Federation of the Red Cross and Red Crescent Societies, Médecins Sans Frontières and UNICEF. Gavi, the Vaccine Alliance, provides funding for the stockpile.

    WHO and the Africa Centres for Disease Control and Prevention (Africa CDC) welcome the allocation of vaccines to the DRC. 

    Against the backdrop of the ongoing outbreak, and based on the available evidence, WHO and Africa CDC support DRC's focus on protecting the people of DRC and using a community-led approach, which empowers communities to play a central role in the response.

    Africa CDC and WHO are united in support of the Government of the DRC, to protect affected communities, save lives and bring the Bundibugyo Ebola outbreak to an end, while generating the scientific evidence needed to strengthen Africa's preparedness for future outbreaks.

Note to editors

    The International Coordinating Group (ICG) on Vaccine Provision was established in 1997, following major outbreaks of meningitis in Africa, as a mechanism to manage and coordinate the provision of emergency vaccine supplies and antibiotics to countries during major outbreaks. 

    The partners and founding institutions are the International Federation of the Red Cross and Red Crescent Societies, MSF, UNICEF and WHO. 

    The core mandate of the ICG is to make available and ensure equitable access to licensed vaccines for cholera, meningitis, yellow fever, and Ebola virus disease during outbreaks. 

    Ebola vaccine stockpile: 

        The ICG has managed the emergency stockpile of Ebola vaccine since January 2021, which was created as an additional tool to control outbreaks of Ebola virus (previously called Zaire ebolavirus). 

        Since the establishment of ICG Ebola mechanism in 2021 until July 2026, over 56 000 doses of Ervebo vaccine have been allocated to respond to Ebola virus outbreaks in DRC. 

        A further 167 000 doses have been used in preventive campaigns for health and frontline workers in DRC, Guinea-Bissau, Kenya, Sierra Leone and Uganda.

Source: 

Link: https://www.who.int/news/item/20-08-2026-who-and-africa-cdc-welcome-the-allocation-of-ebola-vaccines-to-the-democratic-republic-of-the-congo

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The return of #H1N1: Reemergence of the #influenza virus A subtype H1N1 in 1977

 

Abstract

Four major influenza pandemics and two notable outbreaks have been recorded since 1900. This paper discusses the history of the 1977 influenza virus A H1N1 outbreak and re-emergence, often referred to as the “Russian flu” or the “red flu". We describe the likely events leading to the outbreak, including a brief history of the 1976 H1N1 outbreak in a military base in the United States. We reconstruct the spread of the H1N1 virus across the globe in 1977–1978 and discuss the epidemiology of the outbreak. We describe the likely origins of this unusual outbreak mainly affecting young people, including opinions and evidence pointing towards an unnatural origin. Finally, we outline the vaccines developed and vaccination campaigns that were carried out to combat the outbreak.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0264410X26007723?via%3Dihub

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A novel candidate #vaccine virus derived from #Japan's first #mammalian case of clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza virus

 

Abstract

The development of candidate vaccine viruses (CVVs) for pre-pandemic preparedness requires attenuation of pathogenicity while maintaining immunogenicity. In this study, we developed and characterized NIID-002, a reassortant virus derived from A/Ezo red fox/Hokkaido/1/2022 (H5N1; clade 2.3.4.4b), to evaluate its suitability as a candidate vaccine. NIID-002 exhibited markedly reduced pathogenicity compared with its parental strain, while retaining broad antigenic reactivity and protein yield comparable to other clade 2.3.4.4b CVVs. In mammalian models, NIID-002 demonstrated strong attenuation, causing no lethal infection in mice and only minimal weight loss with limited viral replication in ferrets. Antisera raised against NIID-002 reacted broadly with recent wild-type H5N1 isolates, suggesting potential broad protection. Protein yield analysis confirmed a production efficiency comparable to that of other CVVs within the same clade, supporting its feasibility for large-scale vaccine manufacturing. Overall, NIID-002 fulfills the key requirements for the pandemic preparedness of CVV, combining reduced pathogenicity, broad antigenic reactivity, and adequate production efficiency. These findings highlight its potential as a candidate H5N1 vaccine and underscore the continued need for surveillance and refinement of influenza vaccine strategies to address evolving viral threats.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008571?via%3Dihub

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High rates of #SARS-CoV-2 #reinfection in residents of long term care facilities despite robust #spike-specific #immunity following serial #vaccination

 

Abstract

Older adult residents of long-term care facilities (LTCFs) suffered high rates of mortality during the initial stages of the COVID-19 pandemic but their clinical risk has decreased markedly following vaccination. Here we determined humoral and cellular immunity following delivery of a 5th vaccine dose, an mRNA spike B1:BA.1 bivalent vaccine, to care home residents. The delivery of a 5th vaccine elicited a plateau of spike-specific immunity that remained broadly stable over 100 days in almost all people. Despite this, 15% of residents had a primary infection and 30% became reinfected during 6-months of follow up. These findings reveal that serial vaccine delivery can establish robust systemic spike-specific immune responses in frail older people but that this does not reliably prevent SARS-CoV-2 reinfection. As such, additional approaches should be considered to reduce reinfection risk in this vulnerable population group.

Source: 

Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354079

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