ETIDIOH - NEW

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

  Abstract The wildlife reservoir and spillover mechanisms of Ebola virus remain elusive despite extensive research efforts in endemic areas. This study employed a One Health approach to examine the virus’ circulation in wildlife and the associated human exposure risks in the Tshuapa province of the Democratic Republic of the Congo . We screened 1049 samples from 919 animals , predominantly small mammals , collected in 2021, and 380 samples from inhabitants of Inkanamongo village, the site of an Ebola virus disease outbreak in 2014. These samples were screened for evidence of current (RNA) or past (IgG antibodies) Ebola virus infections. We also conducted interviews with 167 individuals in the surrounding districts to assess their interactions with wildlife . While no Ebola virus RNA was detected in the wildlife samples , anti-orthoebolavirus IgG antibodies were found in 13 bats and 38 rodents . Among the human participants , 120 individuals had IgG antibodies against at least 1 or...

  Abstract Influenza A virus (IAV) can infect a wide range of hosts, including wild and domestic pigs . Swine play an important role in influenza evolution and epidemiology due to their ability to get infected with both avian and human influenza viruses, potentially leading to reassorted virus variants . Interactions at the wild-domestic swine interface have been documented on multiple occasions, raising concern about pathogen transmission and the emergence of novel influenza strains. This study investigates the occurrence and subtypes of IAV infecting invasive wild pigs in Alberta, Canada . A total of 267 wild pigs were captured between 2021–2024. Exposure to IAV was initially detected by cELISA , with further confirmation of exposure to the H5Nx virus by hemagglutination inhibition (HI) and virus neutralization (VN) assays. Although no IAV genetic material was detected by qPCR , the seropositive samples by cELISA (4.17%; 5/120) coincided with the 2022–2024 highly pathogenic avian...

  Abstract Background :  Monitoring antigenic drift in human influenza A viruses is essential for vaccine strain selection and ensuring protection against circulating strains. Antigenic drift is traditionally assessed using ferret antisera , which provide monospecific responses , and human vaccinee sera , which reflect exposure to multiple antigens. In this study we evaluated the pig as an alternative source of antisera to study antigenic drift compared to immune responses in ferrets and humans. We included seasonal influenza A(H1N1pdm09) human viruses that had shown different antigenic characteristics when using ferret or human antisera.  Methods :  Pairs of pigs were inoculated with six human A(H1N1)pdm09 viruses circulating between 2019 and 2023, a period of marked antigenic drift. Pig and ferret antisera were analysed by hemagglutination inhibition (HI) and virus neutralization (VN) assays.  Results :  Pigs were successfully infected with all strains, s...

  Abstract In North-East Germany's offshore islands and mainland coast, wild ruminants, boar, and carnivores were tested for H5-HPAI antibodies . Wild ruminants were seronegative ; 3.5% of boar and 12.5-21.9% of carnivores were seropositive , evidencing frequent spillover . Because such events may accelerate mammalian - and ultimately human - adaptation , sustained One-Health monitoring is essential. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared European Union, 101084171 "KAPPA-FLU" Helmholtz Institute for One Health, WiMoPOH Source: BioRxIV,  https://www.biorxiv.org/content/10.1101/2025.09.30.678011v1 ____

  Abstract Background :  Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness.  Methods :  We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada . We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities.  Results :  Among participants with median age 32 (IQR: 15-62) years, 404 ( 70%) had cross-reactive anti-N1 titre ≥10 against H5N1 , with 260 (45%), 182 (32%) and 98 (17%), having titres ≥40, ≥80 and ≥...

  Abstract Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera , measuring ~10,000 total titers . There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution . Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influen...

  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 anti...

  Abstract Background :  Flaviviruses represent a significant worldwide threat to human health and have the potential to emerge and cause outbreaks in non-endemic geographical regions. Ongoing surveillance for these viruses in the United States–Mexican border communities such as El Paso, Texas , is lacking. As a continuing effort to better understand the prevalence and to determine which arboviruses are endemic, the aim of this study was to determine the prevalence rate of specific flavivirus antibody among 910 human umbilical cord blood samples obtained from mothers who delivered newborns in El Paso, Texas. Materials and Methods :  The samples were screened for West Nile virus (WNV) and dengue virus (DENV) IgG antibodies with an enzyme-linked immunosorbent assay and confirmed by a plaque reduction neutralization test for DENV, WNV, Zika virus (ZIKV) and Saint Louis encephalitis virus (SLEV). Results :  Among the 910 samples , 2% were positive for specific IgG antibo...

Summary Background The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections , as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022–23, following a unique period during which virus exposure markedly diminished. Methods This prospective, multicentre, longitudinal, immunoepidemiological surveillance study enroll...

Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes acute respiratory disease after transmission via close contact with camels . In contrast to the incidence of MERS-CoV human infections in the Middle East , MERS-CoV infections in the Horn of Africa have been rarely reported despite the high number of camels and common camel–human interactions in the area. Whether passive cross-sectional sampling misses active human cases is a significant gap in our understanding of MERS-CoV epidemiology and its impact in the Horn of Africa. To address this gap, we conducted a prospective cross-sectional study at Laisamis Catholic Hospital in northern Kenya’s camel pastoralist community . A total of 942 patients with acute respiratory symptoms were enrolled over 18 months (August 2022–February 2024); 54% of these individuals reported frequent contact with camels and consumption of camel products. Testing via reverse transcriptase – polymerase chain reaction ...

Abstract An unprecedented outbreak of Oropouche virus (OROV) is occurring in the Americas, characterized by thousands of confirmed cases and a wide geographical spread, including areas outside the Amazon Basin. Little is known about this neglected arbovirus regarding its pathophysiological aspects and potentially different transmission modes . This study describes the clinical course of a man who returned from a trip to Cuba and presented to our hospital 4 days after the onset of febrile symptoms. The patient was diagnosed with Oropouche fever and was followed for 177 days after the onset of symptoms. We performed a longitudinal investigation of the samples collected from several body sites ( whole blood, serum, urine, and semen ) with the aim of providing further insights into OROV infection dynamics, using the detection of antigenomic RNA as a marker of active viral replication. Clinical samples that were longitudinally collected over the course of OROV infection showed consistently ...

Abstract Recently, cats have emerged as potential incidental hosts for avian and human influenza A viruses (IAVs), including the highly pathogenic avian influenza (HPAI) H5N1 virus. Following an unprecedented outbreak of H5N1 HPAI in cats in Poland in June 2023, we conducted a cross-sectional epidemiological study to assess the seroprevalence of IAV, especially H5Nx , infections in domestic cats. Eight hundred thirty-five serum samples collected in June 2023 were tested using a competitive ELISA for antibodies to IAV nucleoprotein. Positive or doubtful samples were further screened for H5-specific antibodies. The overall seropositivity for IAV was 8.5% (CI 95%: 6.8%, 10.6%; 71/835 cats), and 23/68 IAV-seropositive cats (33.8%) were also seropositive for H5 antigen . Multivariable analysis identified young age (≤8 years) and male sex as significant risk factors for H5 seropositivity, while non-H5-IAV seropositivity was more common in cats aged ≥12 years. These findings suggest different...

Abstract Background :  The experience of the COVID-19 pandemic has differed across continents. We hypothesized that regional differences in SARS-CoV-2 immunity might explain this observation. We therefore established the WWW Consortium in Ghana , W Africa; Jamaica , W Indies ; and W London . Here, we describe the extent to which antibody immunity differs between these geographic locations.  Methods :  The WWW Consortium harmonises across the HERITAGE (Accra, Ghana), WINDFall (Kingston, Jamaica) and Legacy (London, UK) studies, establishing sharing frameworks for samples , metadata, and data; related permissions and oversight; and associated physical and cloud infrastructure. With centralised testing, we performed serological assessments across all three locations at two snapshots in 2024 (April 1st - August 18th; August 19th - December 31st) using high-throughput live virus neutralization and anti-nucleocapsid IgG, including n=763 individuals.  Findings :  We fo...

Abstract The influenza virus neuraminidase (NA) is a promising target for next-generation influenza vaccines but standardized protocols for NA-based serological assays are lacking. Previous studies have demonstrated discordant results from haemagglutination inhibition and live virus microneutralization assays when comparing matched serum and plasma samples . It is therefore important to consider is the choice of serum or plasma samples in assays measuring influenza virus NA-specific antibodies . Here, we compared antibody titres against influenza A and B virus NAs in matched serum and different types of plasma using an enzyme-linked lectin assay (ELLA) and an enzyme-linked immunosorbent assay (ELISA). We observed good correlations between titres determined in serum and different types of plasma. However, there was variable and often poor agreement in the nominal titre values obtained from serum and different kinds of plasma in both ELLA and ELISA, with plasma samples often resulting in...

Abstract Background In Sri Lanka, a high seroprevalence of antibodies against hantaviruses was reported in communities affected by chronic kidney disease of unknown etiology (CKDu). Recently, two rodent-borne hantaviruses , Lanka virus and Anjozorobe virus , were identified in these areas. However, it is unclear which virus is the source of infection in humans, and its pathogenicity is unknown. Methodology/principal findings A total of 181 sera from febrile patients from two CKDu-endemic regions , Girandurukotte and Polonnaruwa, were examined and Lanka virus genome was detected in two IgM-positive febrile patients . Of 76 serum samples from patients with fever of unknown etiology collected during 2016 examined to identify hantavirus genomes, antibodies, and serotypes, 10 were IgG-positive with five of them having IgM also. They were all without clinical features of hemorrhagic fever with renal syndrome , but three patients required treatment in the intensive care unit. A serotyping str...

Abstract Introduction Middle East respiratory syndrome (MERS) is a zoonotic viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV), associated with severe clinical outcomes and high mortality. Objectives Our study examined the kinetics of anti-MERS-CoV IgM and IgG antibodies during the acute and convalescent phases of infection, focusing on their correlations with clinical variables such as age and viral load. Methods Serum samples were collected from PCR-confirmed MERS-CoV patients (n = 23) during both phases and compared to healthy controls (n = 23) using validated ELISA-based assays. Results IgM levels peaked in the acute phase and declined significantly in the convalescent phase , while IgG levels were sustained and markedly higher during recovery . Correlation analyses revealed positive relationships between antibody levels and patient age (acute IgM: r = 0.56, p < 0.01; convalescent IgG: r = 0.59, p < 0.01) and viral loads (acute IgM...

Abstract We confirmed influenza A virus (IAV) by PCR in serum from 18 cows on 3 affected dairy farms in California, USA . Our findings indicate the presence of viremia and might help explain IAV transmission dynamics and shedding patterns in cows. An understanding of those dynamics could enable development of IAV mitigation strategies. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/7/25-0134_article ____

Abstract Highly pathogenic avian influenza (HPAI) H5N1 has been a global concern since its emergence in 1997, causing widespread outbreaks in birds and sporadic human infections . The clade 2.3.4.4b H5N1 virus has rapidly expanded across continents, infecting numerous mammalian species . In 2024, it was detected in dairy cattle for the first time in the U.S., along with human cases following exposure . In Canada , the first human case of this avian influenza was reported in a critically ill adolescent in late 2024. No human-to-human transmission has been documented, but concerns persist regarding mutations associated with enhanced virulence and human adaptation . Although seasonal influenza vaccines are not directed against H5N1, studies suggest that pre-existing immunity from prior infections or vaccinations may provide partial protection against severe H5N1 infections through cross-reactive immune response . Given the ongoing circulation of avian influenza and the rise in human infec...

Abstract We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article ____