#Orthopoxvirus #Antibodies in Feral #Mammals in #Mpox #Outbreak Areas, #Nigeria, 2021–2022

 

Abstract

We analyzed tissue and serum samples from 124 wild animals from communities with confirmed mpox cases in Nigeria. Tissue samples were PCR-negative, but serum samples from 8 animals (6.45%)—3 feral cats, 4 giant pouched rats, and 1 shrew—revealed Orthopoxvirus antibodies, suggesting these species as probable reservoirs.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1565_article

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Serologic #Surveillance of Highly Pathogenic Avian #Influenza Virus Subtype #H5 in #Wildlife, Northeast #Germany, 2023–2025

 

Abstract

We tested wild ruminants, boar, and carnivores in northeast Germany for highly pathogenic avian influenza subtype H5 antibodies. Wild ruminants were seronegative, but 3.5% of boar and 12.5%–21.9% of carnivores were seropositive, indicating frequent spillover. Because such events might accelerate mammalian (and ultimately human) adaptation, sustained monitoring remains essential.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1555_article

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#Ocular findings in Northern #Gannets following an #outbreak of high pathogenicity avian #influenza #H5N1

 

Abstract

During 2021-2022, high pathogenicity avian influenza (HPAI) caused mass mortality in wild birds across Europe, with Northern Gannets (Morus bassanus) among the most affected. Following the outbreak, unusual alterations in the species' characteristic pale iris were observed in some individuals. Opportunistically captured gannets on Bass Rock (n=52), selected to represent a range of iris pigmentation, were examined. Slit-lamp biomicroscopy, indirect ophthalmoscopy, rebound tonometry and photography were performed. Iris pigmentation was classified as normal, mottled or black. Eleven birds underwent avian influenza virus (AIV) serology. Histopathology was performed on two eyes. Abnormal iris pigmentation was found in 74% of adult and immature gannets, with 61% affected bilaterally. Additional signs consistent with uveitis were present in 77% of affected birds. Iris pigmentation abnormalities were positively associated with AIV H5 seropositivity (Fishers exact test, P=0.018). Histopathology from affected eyes showed increased melanin deposition and disorganisation, including loss of a distinct anterior layer of melanocytic cells and hypertrophy of melanocytes within the iris stroma. Field conditions limited uniform lighting and concurrent serology. Iris pigmentation changes were associated with prior HPAI exposure and frequently accompanied by signs of uveitis, suggesting iris alterations may indicate past infection and potential chronic sequelae.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.15.718625v1

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

 

Abstract

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

Source: 

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

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#Population #immunity to clade 2.3.4.4b #H5N1 is dominated by anti - #neuraminidase #antibodies

 

ABSTRACT

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)- and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting antibodies were absent, we detected widespread binding and functional NA antibodies against N1 neuraminidases from clade 2.3.4.4b H5N1 viruses. Neuraminidase inhibition (NI) titers were highest against North American D1.1 genotype N1 viruses and correlated strongly with neutralizing activity, whereas HA-binding antibodies did not. An additional N-linked glycosylation site, as found in the NA of a human D1.1 isolate from British Columbia, reduced susceptibility to NI antibodies. Antibodies titer to N5 from H5N5 were low to minimal. These findings indicate that population-level immunity to clade 2.3.4.4b H5 viruses is dominated by NA-directed antibodies, with important implications for pandemic risk assessment.

IMPORTANCE

Understanding how pre-existing human immunity shapes susceptibility to emerging influenza viruses is central to pandemic preparedness. Here, we determined that human sera contain widespread, functional antibodies targeting H5N1 neuraminidase, which correlate with virus neutralization, whereas HA-directed responses are limited. We further show that acquisition of an NA glycosylation site reduces antibody inhibition, highlighting a potential pathway for immune evasion. These results identify neuraminidase-specific immunity as a major immunological barrier to severe H5N1 disease in humans and emphasize the need to incorporate NA antigenicity into influenza surveillance, risk assessment, and next-generation vaccine design.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00445-26

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#Birth #imprinting effects on the #antibody responses of #H7N9 patients from 2013-2018 in #China

 

Abstract

Background

There is an urgent need to understand the immune correlates of protection against avian influenza viruses (AIV), where pre-existing immunity may be limited.

Methods

Here, we characterized the antibody response in 12 severely ill A(H7N9) patients and examined its association with early-life imprinting and clinical outcome.

Results

We find that A(H7N9) patients imprinted with A(H2N2) during early life show minimal H7-IgM and a rapid IgG response across diverse hemagglutinin subtypes. They also have more high avidity H7-antibodies compared to older or younger patients. Early antibody titers against seasonal H1, H3, and conserved stalk domains trend negatively with clinical severity in A(H7N9) infection, while an inverse pattern is observed following severe A(H1N1) infection, potentially suggesting a different mechanism of immune regulation between seasonal and avian influenza virus infections.

Conclusions

These data provide direct serological evidence that birth imprinting profoundly shapes the humoral immune landscape during zoonotic influenza infection and may influence subsequent disease outcome.

Source: 

Link: https://www.nature.com/articles/s43856-026-01554-1

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#MERS #Coronavirus–Specific T-Cell Responses in Dromedary #Camel #Abattoir #Workers in #Nigeria Suggests Frequent Zoonotic #Spillover

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is assessed to have high pandemic risk, and dromedary camels are the source of zoonotic spillover. More than 75% of MERS-CoV–infected dromedary camels are found in Africa, but no zoonotic disease has been reported from Africa where there is little awareness of MERS-CoV as a potential cause of respiratory disease. Antibody responses are a poor indicator of mild infection. We found that 47 of 60 (78%) dromedary camel abattoir workers in Kano, Nigeria, had MERS-CoV–specific T-cell responses while none of 18 controls did, suggesting that zoonotic infection is common in camel-exposed individuals in Africa.

Source: 

Link: https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiag095/8504072?redirectedFrom=fulltext

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Population #immunity to clade 2.3.4.4b #H5N1 is dominated by anti-neuraminidase #antibodies

 

Abstract

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)- and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting antibodies were absent, we detected widespread binding and functional NA antibodies against N1 neuraminidases from clade 2.3.4.4b H5N1 viruses. Neuraminidase inhibition (NI) titers were highest against North American D1.1 genotype N1 viruses and correlated strongly with neutralizing activity, whereas HA-binding antibodies did not. An additional N-linked glycosylation site, as found in the NA of a human D1.1 isolate from British Columbia, reduced susceptibility to NI antibodies. Antibodies to N5 from H5N5 were minimal. These findings indicate that population-level immunity to clade 2.3.4.4b H5 viruses is dominated by NA-directed antibodies, with important implications for pandemic risk assessment.

Competing Interest Statement

The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines influenza virus vaccines and influenza virus therapeutics which list FK as co-inventor and FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Castlevax, to develop SARS-CoV-2 vaccines. VS is listed on the patent for the SARS-CoV-2 serological assay. FK is co-founder and scientific advisory board member of Castlevax. FK has consulted for Merck, GSK, Sanofi, Gritstone, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development.

Funding Statement

This work was funded through the NIAID Centers for Excellence in Influenza Research and Response (75N93021C00014 as well as option APOLLO Option 12A) and through philanthropic support from Titos Vodka. Work at the Medical University of Vienna was funded by Institutional Funds.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.02.10.26346014v1

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Detection of Avian #Influenza #H5–Specific #Antibodies by Chemiluminescent Assays

 

Abstract

We evaluated 2 electrochemiluminescence serologic assays to detect avian influenza H5 antibodies. Both assays identified H5 antibodies from both serum and dried blood spots and had strong specificity and minimal cross-reactivity in human and avian samples. Such assays can support populationwide serologic surveys aimed at assessing population-level immunity.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/1/25-1117_article

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Development of a multi-species #luciferase-based double #antigen #ELISA for the detection of #antibodies against #Influenza A virus #H5 clade 2.3.4.4b

 

Abstract

The highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 represent a major threat to animal and public health. The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, massive losses and a high frequency of spillover events to unexpected novel mammalian hosts such as dairy cows. The global H5N1 situation raises serious concerns about zoonotic risks due to effective mammal-to-mammal transmission. Therefore, it is critical to increase surveillance intensity of a broadened species range, particularly at the human-animal interface. For this purpose, reliable and cost-effective serological tools that are easy to perform and suitable for high-throughput screenings are critically needed. The newly developed double antigen ELISA format employing a luminescence-based detection technology has demonstrated to comply with such prerequisites. The assay allowed the detection of H5-specific antibodies even early after infection or vaccination in a wide range of birds and mammals including humans. It further demonstrated superior analytical sensitivity and high specificity for antibodies directed against H5 hemagglutinin of clade 2.3.4.4b as no cross-reactivity with other hemagglutinin subtypes was observed. Thus, the assay represents a valuable contribution to existing serological diagnostic tests for a clade-optimized detection of influenza A virus antibodies in a broad range of species.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.05.697617v1

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#Serological evidence of concurrent #Lassa virus and #SARS-CoV-2 #exposure in #Ghana- a cross-sectional study

 

Abstract

Background

The COVID-19 pandemic has exposed vulnerabilities in infectious disease surveillance, especially in West Africa where endemic viruses including Lassa fever persist. The overlapping clinical symptoms of these two infections create diagnostic challenges and the possibility of undetected co-infections.

Methods

A retrospective cross-sectional study was conducted using archived serum samples from a nationwide SARS-CoV-2 seroprevalence survey in Ghana. 434 samples across six regions were tested for SARS-CoV-2 total antibodies (IgG/IgM) using the WANTAI ELISA kit and Lassa virus IgG using ReLASV Pan-Lassa-NP-IgG ELISA.

Results

SARS-CoV-2 antibody prevalence was 64.29% (n = 279) and Lassa virus IgG prevalence was 20.28% (n = 88). Of the cohort of subjects who were seropositive for SARS-CoV-2, 20.79% were also seropositive for LASV IgG. Multivariate analysis revealed household size as a strong risk factor of dual exposure. Individuals from medium-sized households (4–6 persons) (aOR = 8.78, 95% CI: 1.18–65.56, p = 0.034) and large households (≥ 7 persons) (aOR = 12.90, 95% CI: 1.99–83.40, p = 0.007) had significantly increased odds of dual seropositivity compared to small households. Regional variations were observed, with Greater Accra showing significantly lower odds of dual seropositivity (aOR = 0.13, 95% CI: 0.03–0.51, p = 0.004) compared to Ashanti Region.

Conclusion

This study provides serological evidence of SARS-CoV-2 and Lassa virus concurrent exposure in Ghana during the COVID-19 pandemic. This finding suggests large household size as a key driver of dual viral exposure and calls for integrated surveillance systems and targeted interventions in large household settings to reduce concurrent transmission of viruses with pandemic potential.

Source: 

Link: https://link.springer.com/article/10.1186/s12879-025-12385-1

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Pre-existing cross-reactive #immunity to highly pathogenic avian #influenza 2.3.4.4b #H5N1 virus in the #USA

 

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 2.3.4.4c vaccine can elicit cross-reactive neutralizing antibodies to 2.3.4.4b A(H5N1) viruses. Understanding population susceptibility is essential for pandemic preparedness.

Source: 

Link: https://www.nature.com/articles/s41467-025-66431-2

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Assessing #Ebola virus circulation in the Tshuapa province (#DRC): A #OneHealth #investigation of wildlife and #human interactions

 

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 orthoebolavirus antigen, with 12 showing seropositivity for 2 antigens of the same orthoebolavirus, despite not having a prior Ebola disease diagnosis. Furthermore, the majority of respondents reported frequent visits to the forest to hunt a variety of wild animals, particularly ungulates and rodents, which could account for occasional viral spillovers. The absence of active Ebola virus circulation in wildlife may reflect seasonal patterns in reservoir ecology, as those observed in bats. Similarly, seasonal human activities, such as hunting and foraging, may result in periodic exposure risks. These findings highlight the importance of continuous, multidisciplinary surveillance to monitor changes in seasonal spillover risks.

Author summary

Since its discovery in 1976 in the Democratic Republic of Congo (DRC), Ebola virus (EBOV) has caused more than 20 outbreaks in humans, with fatality rates as high as 90%. While the virus is believed to have an animal origin, naturalist reservoir and the mechanisms of transmission to humans remain poorly understood. Gaining insight into which species may harbour the virus and how transmission occurs is essential to predict and prevent future outbreaks. In this study, we investigate EBOV exposure in wildlife and humans in a region of the DRC with a documented history of outbreaks. Although we did not detect active infection in animals, we found serological evidence of prior exposure in several bat and rodent species, as well as among local residents. Interviews with community members revealed frequent contact with wildlife through hunting and handling, practices that could elevate the risk of animal-to-human transmission. These findings offer new clues about possible EBOV reservoirs and highlight the role of human behaviours in facilitating facilitate spillover events. Our results underscore the need for continued, integrated surveillance to improve understanding of Ebola virus ecology and to help reduce the risk of future Ebola outbreaks in endemic regions.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013628

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Serological #Evidence of Highly Pathogenic Avian #Influenza #H5N1 in Invasive Wild #Pigs in Western #Canada

 

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 influenza virus (HPAI) H5N1 epizootic in Alberta, which involved outbreaks in wild species and domestic birds. These findings, combined with the epidemiological context, suggest interspecies transmission of HPAI H5N1 clade 2.3.4.4b to wild pigs. These results highlight the potential role of wild pigs as a new host in Canada and emphasize the need for continued surveillance of IAV in wild pig populations to assess the risk of spillover events at the wildlife, livestock, and human interfaces.

Source: 

Link: https://onlinelibrary.wiley.com/doi/10.1155/tbed/2720469

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Post-infection #pig and #ferret antisera show similar #antigenic profiles for #human #influenza #H1N1pdm09 viruses

 

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, shedding virus and producing antibody responses, confirming their susceptibility to human influenza A viruses. Antigenic reactivity of pig antisera was qualitatively comparable to ferret antisera in both HI and VN assays, although maximum homologous antibody titres were significantly higher in ferrets. The antisera raised against viruses in circulation in 2019 and before, exempified by A/Guangdong-Maonan/SWL1536/2019, clade 5a.1, were clearly differentiated by both ferret and pig antisera from those in clade 5a.2 and its derivatives that became predominant. 

Conclusions: 

Ferrets and pigs showed comparable responses and both distinguished clade 5a.1 from clade 5a.2. However, neither model recognised antigenically drifted variants from 2019/2022, including subclades 5a.2 C, 5a.2a C.1/C.1.9, and .5a.2a.1 C.1.1/D, which were distinguishable using human post-vaccination antisera.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X511134/1 , BBS/E/PI/230002A, BBS/E/PI/230002B, BBS/E/PI/23NB0004, BBS/E/PI/23NB0003, BB/Y007298/1

Medical Research Council, https://ror.org/03x94j517, CC1114

Cancer Research UK, CC1114

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.10.30.685573v1

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Opportunity Drives #Spillover: Serological #Surveillance across #Carnivores, #Omnivores and #Herbivores in an #HPAIV #H5 Hotspot in North-East #Germany, 2023-2025

 

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

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Cross-reactive #neuraminidase inhibition #antibodies against #H5N1 by consecutive #influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, #Canada

 

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 ≥160, respectively. H5N1 titres were consistently lower but strongly associated with H1N1pdm09 (r=0.86; 95%CI:0.82-0.89). Geometric mean titres against H1N1pdm09 and H5N1 peaked among young adults born 1997-2003 (427.9, 100.8), declining to lows among young children born 2015-2023 (20.7, 6.8) and middle-aged adults born 1957-1967 (25.1, 10.7), increasing to similar secondary peak among older adults born pre-1947 (387.3, 81.0). 

Conclusions: 

A substantial proportion of the population has pre-existing, cross-reactive anti-N1 antibodies against H5N1. We interpret variation by age and imprinting cohorts within a unifying hypothesis, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. Our findings have implications for H5N1 and other zoonotic influenza risk assessment.

Competing Interest Statement

DMS is Principal Investigator on grants received to her institution from the Public Health Agency of Canada, Pacific Public Health Foundation, Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research for unrelated work. As the Provincial Health Officer with authority under the emergency provisions of the Public Health Act, BH authorized the provision and analysis of the anonymized sera used in this study; the study was separately reviewed and approved by the UBC Clinical Research Ethics Board and Health Canada-Public Health Agency of Canada Research Ethics Board. No other competing interests were declared.

Funding Statement

This work was supported by the Public Health Agency of Canada (Grant number: 2021-HQ-00067), received by the Institution of DMS. The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.19.25336209v1

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High-throughput neutralization measurements correlate strongly with evolutionary success of #human #influenza strains

 

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 influenza.

Competing Interest Statement

JDB is on the scientific advisory boards of Apriori Bio, Invivyd, Aerium Therapeutics, and the Vaccine Company. JDB consults for GlaxoSmithKline and Pfizer. JDB and ANL receive royalty payments as inventors on Fred Hutch licensed patents related to incorporating barcodes into the influenza genome and viral deep mutational scanning. 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.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, 75N93021C00015, T32AI083203, R01AI165821

Howard Hughes Medical Institute

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.04.641544v2

____

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.

Funding Statement

J.S.B. was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) doctoral training programme grant [grant number BB/M011224/1]. R.S. is funded by a Medical Research Council Impact Accelerator Account grant [grant ref MR/X502674/1]. RG was funded by The Institute for Global Pandemic Planning at the University of Warwick, UK, as part of a philanthropically supported doctoral programme. K.C. was funded via the Medical Research Council doctoral training programme grant [MC_UP_A025_1011]. L.H. was funded by a Defence and Science Technology Laboratory grant [grant ref RQ31692]. U.O. and C.P.T. acknowledge funding from the British Council ISFP scheme [grant number 47650215]. N.C.R. is supported by a Royal Society Dorothy Hodgkin Research Fellowship [grant number DHR00620].

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v1

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Serological #Evidence of #Flavivirus #Infection Among #Mothers of #Newborns in El Paso, #Texas

 

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 antibody to DENV, 4.4% to WNV, 0.1% to SLEV, and 0.0% for ZIKV antibody. The results confirmed the local transmission of WNV and supported a low prevalence rate for DENV, and this was the first reported serological evidence of SLEV infection in the El Paso community.

Conclusion: 

The interpretation of the public health significance of these observations supported previous findings of ongoing transmission of WNV and suggested the possibility of DENV transmission and re-emergence of SLEV in the community. Therefore, prospective studies are needed to obtain a more conclusive understanding of the prevalence of flaviviruses in the El Paso community.

Source: Vector-Borne and Zoonotic Diseases, https://www.liebertpub.com/doi/abs/10.1177/15303667251367518

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