Attachment and #replication of clade 2.3.4.4b #influenza #H5N1 viruses in #human respiratory #epithelium: an in-vitro study

 

Summary

Background

Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans. Cross-species transmission events to mammals, including humans, in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells. Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response.

Methods

In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1Gull2022, H5N1Polecat2022, and H5N1Bovine2024) in comparison with previously studied 2.1.3.2 H5N1 (H5N12005) and a seasonal H3N2 virus. First, we compared virus attachment patterns by virus histochemistry. Second, we investigated the infection and replication efficiency, and innate immune responses in infected human respiratory epithelium in vitro. Third, we measured polymerase complex activity using a minigenome assay.

Findings

Clade 2.3.4.4b viruses and H5N12005 virus differed by five amino acids located near the receptor binding site of the haemagglutinin. All clade 2.3.4.4b viruses attached more efficiently to cells of the human upper and lower respiratory tract compared with H5N12005 virus. All clade 2.3.4.4b viruses replicated in human nasal and tracheobronchial respiratory epithelium cultures. In the tracheobronchial respiratory epithelium cultures, H5N1Gull2022 virus replicated more efficiently than H5N12005 virus (p=0·0050) and reached titres similar to H3N22003 virus. Polymerase complex activity of H5N1Gull2022 virus was not significantly different from that of H5N12005 and was significantly lower compared with H3N22003 virus (p≤0·0001). Infection with H5N1Gull2022 virus induced a broader antiviral immune response than H5N12005 virus.

Interpretation

Clade 2.3.4.4b H5N1 viruses have phenotypic characteristics that are different from a clade 2.1.3.2 H5N12005 virus. The ability of clade 2.3.4.4b viruses to attach to and replicate in respiratory epithelium likely contributes to an increased risk for both human infection and virus adaptation to humans.

Funding

The EU, the Dutch Research Council, the Netherlands Organization for Health Research and Development, and the Dutch Ministries of Agriculture, Fisheries, Food Security and Nature, and Health, Welfare and Sport.

Source: 

Link: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(25)00158-2/fulltext

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#Statement on the #antigen #composition of #COVID19 #vaccines (#WHO, Dec. 18 '25)

 

Key points:

-- The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) held its twice-yearly decision-making meeting in December 2025 to review the evolution of SARS-CoV-2, the performance of currently approved COVID-19 vaccines and the implications for COVID-19 vaccine antigen composition.

-- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants.

-- Following this meeting, the TAG-CO-VAC advises vaccine manufacturers that monovalent LP.8.1 is the recommended vaccine antigen.

-- The previously recommended JN.1 lineage (JN.1 or KP.2) antigens remain suitable alternatives and vaccination should not be delayed in anticipation of access to vaccines with the LP.8.1 composition.

-- Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating SARS-CoV-2 variants could also be considered.

-- Vaccination remains an important public health countermeasure against COVID-19. As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE).

The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continues to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants. 

Based on these evaluations, WHO advises vaccine manufacturers and regulatory authorities on the implications for future updates to COVID-19 vaccine antigen composition. 

In May 2025, the TAG-CO-VAC recommended that monovalent JN.1 or KP.2 remain appropriate vaccine antigens and that monovalent LP.8.1 is a suitable alternative vaccine antigen. 

Multiple manufacturers (using mRNA or recombinant protein-based vaccines) have updated COVID-19 vaccine antigen composition to monovalent JN.1 lineage formulations (JN.1, KP.2 or LP.8.1). 

Several of these vaccines have been approved for use by regulatory authorities and have been introduced into vaccination programmes. Previous statements from the TAG-CO-VAC can be found on the WHO website.

The TAG-CO-VAC reconvened on 8-9 December 2025 to review: 

- the genetic and antigenic evolution of SARS-CoV-2; 

- immune responses to SARS-CoV-2 infection and/or COVID-19 vaccination; 

- the performance of currently approved vaccines against circulating SARS-CoV-2 variants; and 

- the implications for COVID-19 vaccine antigen composition.

Evidence reviewed

The published and unpublished evidence reviewed by the TAG-CO-VAC included: 

-- (1) SARS-CoV-2 genetic evolution with additional support from the WHO Technical Advisory Group on Virus Evolution (TAG-VE); 

-- (2) Antigenic characterization of previous and emerging SARS-CoV-2 variants using virus neutralization tests with animal antisera and further analysis of antigenic relationships using antigenic cartography; 

-- (3) Immunogenicity data on the breadth of neutralizing antibody responses elicited by currently approved vaccine antigens against circulating SARS-CoV-2 variants using animal and human sera; 

-- (4) Preliminary clinical immunogenicity data on immune responses following infection with circulating SARS-CoV-2 variants; 

-- (5) Available relative vaccine effectiveness (VE) estimates of currently approved vaccines during periods of JN.1 lineage circulation; and 

-- (6) Preliminary non-clinical and clinical immunogenicity data on the performance of candidate vaccines with updated antigens shared confidentially by vaccine manufacturers with TAG-CO-VAC. 

Further details on the data reviewed by the TAG-CO-VAC can be found in the accompanying data annex. Confidential data reviewed by the TAG-CO-VAC are not shown.

Summary of available evidence

-- There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, limiting the interpretation of epidemiological trends. 

-- Nonetheless, in 2025, SARS-CoV-2 continues to circulate globally, causing severe disease, post COVID-19 condition, and death. 

-- Globally, the majority of COVID-19 deaths continue to occur in individuals aged 65 years and older and those with underlying comorbidities.

-- As of early December 2025, most circulating SARS-CoV-2 variants worldwide remain derived from JN.1. 

-- In most regions, SARS-CoV-2 Variant Under Monitoring (VUM) XFG is the predominant variant among SARS-CoV-2 sequences submitted to GISAID, typically accounting for 70-80% of all variants reported. 

-- In contrast, in several countries in the WHO Western Pacific Region in which SARS-CoV-2 sequencing continues, VUM NB.1.8.1 has been the most recent predominant variant, with XFG detected at lower levels. 

-- VUM BA.3.2, first detected in November 2024, continues to be detected at low levels globally; however, higher levels have been reported in limited geographic areas, particularly in wastewater and clinical samples in Western Australia. 

-- The proportions of JN.1 (Variant of Interest) and all other VUMs (KP.3.1.1 and LP.8.1) are declining and are now detected at low levels.

-- Published and unpublished neutralization data using antisera from naïve mice and hamsters infected with JN.1 or XFG, as well as mice immunized with mRNA vaccine antigens JN.1, LP.1.8.1, NB.1.8.1 or XFG, indicate that recent JN.1-derived variants are antigenically closely related. These variants differ by approximately 1 antigenic unit in cartographic analyses, corresponding to a two-fold-difference in neutralization, with XFG often the most antigenically distant from JN.1 within the JN.1 cluster. In contrast, these antisera showed limited neutralization activity against BA.3.2, indicating that BA.3.2 is antigenically distinct from circulating JN.1-derived variants.

-- Sera collected in 2025 from individuals with prior SARS-CoV-2 infection or COVID-19 vaccination showed a moderate reduction in neutralizing antibody titers against BA.3.2, as compared to those against JN.1 and LP.8.1.

-- Published and unpublished human serological data of pre- and post-vaccination sera from individuals immunized with JN.1 or KP.2 demonstrated significant increases in neutralizing activity against JN.1 and its descendent lineages. Post-vaccination neutralizing antibody titers against NB.1.8.1 and XFG were lower than those against the homologous JN.1 or KP.2 antigens, with even larger reductions observed for BA.3.2.

-- Pre- and post-vaccination sera from individuals immunized with LP.8.1 demonstrated significant increases in neutralizing activity against JN.1 and its descendent lineages, including NB.1.8.1 and XFG. Post-vaccination neutralizing antibody titers against BA.3.2 were lower than against the homologous LP.8.1 antigen and other JN.1-derived variants.

-- Contemporary vaccine effectiveness (VE) estimates are relative (rVE), rather than absolute (comparing vaccinated to unvaccinated individuals), and demonstrate the added or incremental protection of recent vaccination over and above pre-existing infection- and vaccine-derived immunity. Monovalent JN.1 and KP.2 mRNA vaccines demonstrated additional protection—relative to pre-existing immunity—against symptomatic and severe COVID-19. There are currently no studies reporting VE or rVE estimates using monovalent LP.8.1 vaccines.

-- Data shared confidentially with the TAG-CO-VAC by vaccine manufacturers showed that:

- Immunization of naïve mice and mice previously immunized with SARS-CoV-2 variants with monovalent JN.1 elicited high neutralizing antibody titers against JN.1, XEC, LP.8.1, NB.1.8.1. Neutralization titers against XFG were typically lower than those against the homologous immunizing antigen, with further reductions observed against BA.3.2.

- Immunization of naïve mice and mice previously immunized with SARS-CoV-2 variants with monovalent LP.8.1 induced high neutralizing antibody titers against the homologous antigen, JN.1, NB.1.8.1 and XFG. Reductions in antibody titers were consistently observed against BA.3.2.

-- In humans, vaccination with monovalent JN.1 elicited robust neutralizing antibody responses against JN.1, XEC, LP.8.1 and NB.1.8.1. As observed in mice, post-monovalent JN.1 vaccination neutralizing antibody titers against XFG and BA.3.2 were lower than those against the homologous JN.1 antigen. Vaccination with 8.1 induced strong increases in neutralizing antibody titers against JN.1, LP.8.1, NB.1.8.1 and XFG. As in mice, post-monovalent LP.8.1 vaccination neutralizing antibody titers against BA.3.2 were lower than those against the homologous LP.8.1 antigen.

-- Overall, LP.8.1 as a vaccine antigen offers modestly but significantly increased cross-reactive antibody responses to currently circulating JN.1-derived variants, as compared to monovalent JN.1 or KP.2 vaccines.

The TAG-CO-VAC acknowledges several limitations of available data: 

-- There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, as well as in genetic/genomic surveillance of SARS-CoV-2 globally, including low numbers of samples sequenced and limited geographic diversity. The TAG-CO-VAC strongly supports the ongoing work of the WHO Coronavirus Network (CoViNet) and the Global Influenza Surveillance and Response System (GISRS) to address this information gap.

-- The timing, specific mutations and antigenic characteristics of emerging and future variants are difficult to predict, and the potential public health impact of these variants remain unknown. While most circulating variants are currently derived from JN.1, there are long branch saltation variants, such as BA.3.2, that are currently detected in low proportions of SARS-CoV-2 variants sequenced globally. Available data indicate that BA.3.2 does not currently exhibit a clear fitness advantage over JN.1-derived variants; however, its future evolutionary potential remains uncertain. These variants will continue to be monitored and/or characterized and the TAG-CO-VAC strongly supports the ongoing work of the TAG-VE. 

-- Although neutralizing antibody titers have been shown to be important correlates of protection from SARS-CoV-2 infection and of estimates of vaccine effectiveness, there are multiple components of immune protection elicited by infection and/or vaccination. Data on the immune responses following JN.1 descendent lineage infection or monovalent JN.1, KP.2 or LP.8.1 vaccination are largely restricted to neutralizing antibodies. Data and interpretation of other aspects of the immune response, including cellular immunity, are limited. 

-- Immunogenicity data against currently circulating SARS-CoV-2 variants are not available for all COVID-19 vaccines. 

-- Estimates of rVE against recently circulating JN.1 variants are limited in terms of the number of studies, geographic diversity, vaccine platforms evaluated, populations assessed, duration of follow-up, and contemporary comparisons of vaccines with different antigen composition.

Recommendations for COVID-19 vaccine antigen composition

-- Monovalent LP.8.1 (NextStrain: 25A; GenBank: PV074550.1; GISAID: EPI_ISL_19467828) is the recommended COVID-19 vaccine antigen.

-- As vaccination should not be delayed in anticipation of access to vaccines with an LP.8.1 composition, previously recommended JN.1 lineage (JN.1 or KP.2) antigens remain suitable alternatives.

Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating SARS-CoV-2 variants could also be considered.

As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO SAGE.

Further data requested

Given the limitations of the evidence upon which the recommendations above are derived and the anticipated continued evolution of the virus, the TAG-CO-VAC strongly encourages generation of the following data (in addition to the types of data outlined in September 2025): 

-- Immune responses and clinical endpoints (i.e. VE and/or comparator rates of infection and severe disease) in varied human populations who receive currently approved COVID-19 vaccines against emerging SARS-CoV-2 variants, across different vaccine platforms.

-- Strengthened epidemiological and virological surveillance, as per the Standing Recommendations for COVID-19 in accordance with the International Health Regulations (2005), to determine if emerging variants are antigenically distinct and able to displace circulating variants.

-- Strengthened epidemiological surveillance to characterize disease severity in immunologically naïve and/ or immature individuals (i.e. birth cohorts).

-- Non-clinical and clinical immunogenicity data against circulating SARS-CoV-2 variants for vaccine candidates with different SARS-CoV-2 antigens, such as BA.3.2.

-- As previously stated, the TAG-CO-VAC continues to encourage the further development of vaccines that may improve protection against infection and reduce transmission of SARS-CoV-2.

-- The TAG-CO-VAC will continue to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants. The TAG-CO-VAC will also continue to reconvene every six months, or as needed, to evaluate the implications for COVID-19 vaccine antigen composition. At each meeting, recommendations to either maintain current vaccine composition or to consider updates will be issued. Prior to each meeting, the TAG-CO-VAC will publish an update to the statement on the types of data requested to inform COVID-19 vaccine antigen composition deliberations.

Source: 

Link: https://www.who.int/news/item/18-12-2025-statement-on-the-antigen-composition-of-covid-19-vaccines

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The #epidemiology of #pathogens with #pandemic potential: A review of key #parameters and clustering analysis

 

Highlights

• Epidemiological parameters differ by pathogen and by setting.

• Unsupervised machine learning classifies pathogens into distinct epidemiological archetypes.

• Pathogens can be allocated into defined groups outlining plausible parameter ranges across epidemiologically similar pathogens.

Abstract

Introduction

In the light of the COVID-19 pandemic many countries are trying to widen their pandemic planning from its traditional focus on influenza. However, it is impossible to draw up detailed plans for every pathogen with epidemic potential. We set out to try to simplify this process by reviewing the epidemiology of a range of pathogens with pandemic potential and seeing whether they fall into groups with shared epidemiological traits.

Methods

We reviewed the epidemiological characteristics of 19 different pathogens with pandemic potential (those on the WHO priority list of pathogens, different strains of influenza and Mpox). We extracted data on key parameters (reproduction number serial interval, proportion of presymptomatic transmission, case fatality risk and transmission route) and applied an unsupervised learning algorithm. This combined Monte Carlo sampling with ensemble clustering to classify pathogens into distinct epidemiological archetypes based on their shared characteristics.

Results

From 154 articles we extracted 302 epidemiological parameter estimates. The clustering algorithms categorise these pathogens into six archetypes (1) highly transmissible Coronaviruses, (2) moderately transmissible Coronaviruses, (3) high-severity contact and zoonotic pathogens, (4) Influenza viruses (5) MERS-CoV-like and (6) MPV-like.

Conclusion

Unsupervised learning on epidemiological data can be used to define distinct pathogen archetypes. This method offers a valuable framework to allocate emerging and novel pathogens into defined groups to evaluate common approaches for their control.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1755436525000702?via%3Dihub

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#Airway #organoids reveal #patterns of #Influenza A tropism and #adaptation in #wildlife species

 

Abstract

Identifying animal species that are susceptible to the plethora of existing and emerging viruses is critical for predicting and containing disease outbreaks. Current efforts to assess viral tropism largely rely on experimental infection models, but such experiments are logistically and ethically infeasible for many wildlife species. To tackle this challenge, we developed a panel of airway organoids from ten taxonomically diverse wildlife and livestock species and evaluated their susceptibility to influenza viruses of mammalian (pH1N1) and avian (H5N1) origin. Our analyses revealed large species-specific differences in infection rate and cytopathogenicity that aligned with known in vivo data and field observations. Furthermore, we demonstrated that this organoid panel can serve as a powerful tool to elucidate receptor-binding mechanisms, viral dynamics, and early host adaptation in poorly characterized animal species. In summary, this work provides a robust and ethically viable approach for evaluating viral tropism and adaptation in wildlife species, and fills a critical gap in current pandemic preparedness, zoonotic disease surveillance, and wildlife conservation efforts.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Ministerio de Ciencia, Innovación y Universidades, https://ror.org/05r0vyz12, PLEC2022-009171, RYC2021-033035-I, PID2023-147498OB-I00, JDC2023050389-I

European Commission, HORIZON-HLTH-2021 CORONA-01, HORIZON-HLTH-2023-DISEASE-03

CERCA Institution, https://ror.org/01bkbaq61

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.17.694819v1

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Isolation and subtyping of avian #influenza A virus from wild #birds in #Khartoum, #Sudan

 

Abstract

Avian influenza (AI) is a significant disease affecting chickens and other avian species. Wild birds are thought to contribute to the virus transmission. The present study intends to explore the existence of AI type A virus in wild birds at the Six April Zoo, Khartoum State, Sudan. A total of 42 cloacal and tracheal swabs were collected from clinically healthy individuals belonging to five different wild bird species. The selected wild bird species were Common crane Grus grus, Sudan crowned crane Balearica pavonina, Helmeted guinea fowl Numida meleagris, Duck sp. Anatidae and Chestnut-billed sand grouse Pterocles exustus. Swabs were examined for AI virus antigen using the agar gel immunodiffusion (AGID) test, and all tested swabs produced positive results. The swab samples were inoculated into embryonated chicken eggs. The isolated virus was identified by AGID test and polymerase chain reaction. The virus was isolated from swabs collected from Grus grus, Balearica pavonina, Numida meleagris, Duck sp. Anatidae and Pterocles exustus. Subtyping of the isolated viruses was performed using reverse transcriptase-polymerase chain reaction, which identified the H5 subtype.

Source: 

Link: https://ojvr.org/index.php/ojvr/article/view/2228

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#MERS-COV in the Middle East, a #OneHealth #concept approach

 

Abstract

The MERS-COV virus is a zoonotic coronavirus that emerged in 2012 in KSA and caused viral illness with a case fatality rate up to 35 %. Over a decade later, the virus is still evolving and circulating. The aim of this review is to discuss the current epidemiology of MERS-COV both in humans and animals, during and post the COVID-19 pandemic. We have found that MERS-COV is still evolving in camels with new lineages being detected in Saudi Arabia. Although the number of human cases has decreased, there is a gradual resurgence in the number of cases. Furthermore, many cases are being reported without exposure to camels and/or raw products, nor contact with known human cases. This necessitates global efforts in the surveillance of asymptomatic carriers in the community, role of unknown animal reservoirs in the virus spread if any, as well as extensive genomic surveillance of the virus. This is in order to unveil and assess the genetic changes that the virus is undergoing and their according effect on the viral fitness, tropism, and virulence. These efforts are crucial for potential future pandemic preparedness, understanding the modes of transmission, as well as drug and vaccine development for MERS-COV.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S2352771425003180?via%3Dihub

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#Poland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

By Andrey Gulivanov - Taiga bean goose, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=161227833

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A wild Bean Goose in Łódzkie Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7127

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Efficacy of ProC6C-AlOH/Matrix-M against #Plasmodium falciparum #infection and #mosquito #transmission: a phase 2, randomised, controlled human malaria infection study

 

Summary

Background

An investigational multistage malaria vaccine, ProC6C, based on distinct Plasmodium falciparum epitopes from the sporozoite stage (P falciparum circumsporozoite protein [PfCSP]) and the transmission stages (Pfs230 and Pfs48/45), adsorbed to aluminium hydroxide (AlOH) and adjuvanted with Matrix-M adjuvant (ProC6C-AlOH/MM), has previously shown safety and immunogenicity in phase 1 studies. We aimed to study vaccine efficacy, safety, and immunogenicity in African adults with lifelong malaria exposure.

Methods

This randomised controlled double-blind vaccination and controlled human malaria infection (CHMI) study was conducted in Sotuba, a peri-urban setting in Mali. Healthy adults (aged 18–50 years), who were malaria experienced and met eligibility criteria, were randomly assigned (1:1) to receive three intramuscular injections of ProC6C-AlOH/MM (100 μg ProC6C and 50 μg Matrix-M adjuvant) or Verorab rabies vaccine (control) 4 weeks apart. Randomisation was done in randomly permuted blocks (random varying block size of two and four) using R Statistical Software (randomizr and blockrand). The content of syringes was masked to ensure blinding and only those responsible for vaccine preparation were unblinded. 94 days after the last vaccination, all participants still in the study underwent CHMI by intradermal inoculation of 22 500 P falciparum sporozoites (Sanaria PfSPZ Challenge [NF54]). Primary outcomes were time to blood-stage infection (quantitative PCR detection of P falciparum, with vaccine efficacy defined as 1 – Cox hazard ratio in the per-protocol population) and vaccine safety and tolerability (in those who were randomly assigned and received at least one vaccination). The trial was registered in the Pan African Clinical Trial Registry (PACTR202404598604620).

Findings

On March 20, April 15, and May 9, 2024, 34 participants (15 males, 19 females) received their vaccinations (n=17 ProC6C-AlOH/MM and n=17 control vaccine). The vaccinations were well tolerated, with 13 (76%) of 17 ProC6C-AlOH/MM recipients experiencing at least one adverse event, almost all of which were mild, compared with three (18%) of 17 control vaccine recipients. On Aug 11, 2024, 94 days after the last dose of vaccine, 32 of 34 participants underwent CHMI, of whom 19 (59%) developed P falciparum parasitaemia by day 28 post-CHMI initiation (13 of 16 in the control group and six of 16 in the ProC6C-AlOH/MM group). In those that became parasitaemic, the median time to positivity was delayed in ProC6C-AlOH/MM recipients by 2 days (14 days ProC6C-AlOH/MM, 12 days control; p=0·049). In the per-protocol time-to-event analysis, vaccine efficacy was 76% (95% CI 36–91, p=0·0022). By proportional analysis (1 – risk ratio) the vaccine efficacy was 54% (95% CI 9–77, p=0·029).

Interpretation

This is the first clinical trial of an anti-PfCSP subunit vaccine that has shown greater than 50% vaccine efficacy against CHMI at 12 weeks after the last vaccine dose, associated with a novel, strong, and mechanistically plausible correlate of protection. Following age de-escalation, future phase 2 studies with ProC6C should therefore assess vaccine efficacy against naturally acquired clinical malaria and onward transmission in the target population, preschool-aged and primary-school-aged children.

Funding

European & Developing Countries Clinical Trials Partnership (EDCTP2 programme) and Gates Foundation.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00664-4/abstract?rss=yes

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Immunological and virological #questions for #H5N1 #pandemic emergence

 

Abstract

Zoonotic spillover of influenza A viruses into humans has repeatedly triggered pandemics throughout history. Since their emergence in the 1990s, H5N1 influenza viruses have significantly expanded their geographical range and host species, raising global concern about the potential for sustained human-to-human transmission. In this review, we examine the virological characteristics of currently circulating H5N1 strains, key molecular barriers limiting their spread among humans, and critical areas of future research to mitigate the ongoing H5N1 panzootic and prevent future pandemics.

Source: 

Link: https://academic.oup.com/immunohorizons/article/9/SI/vlaf062/8381786

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Mass #mortality at #penguin mega-colonies due to avian cholera confounds #H5N1 HPAIV #surveillance in #Antarctica

 

Abstract

In the austral summer 2023/2024, H5N1 high pathogenicity avian influenza virus (HPAIV) was reported for the first time in Antarctica. Concerns of HPAIV causing high mortality of seabirds and mammals prompted immediate efforts to track its spread and impact on endemic wildlife. In March 2024, we visited the Danger Islands archipelago, that hosts two mega-colonies of Adélie penguins, and observed an unusual mortality estimated in thousands of Adélie penguins and other species. Swabs and tissues were collected for molecular detection of infectious agents from 49 carcasses, and additional tissues for histology from a selection of 9 carcasses. We unexpectedly detected Pasteurella multocida DNA in 46 of 49 individuals, and diagnosed avian cholera, and not HPAI, as the cause of death of most of these animals. By metagenomics, we retrieved the genomic sequences of the Pasteurella multocida strain which caused the epizootic, and the phylogenetic analysis showed a close relation with strains previously reported in the Southern Ocean area. This study confirms avian cholera as a relevant cause of mortality in the Antarctic region, and overall highlights the importance of considering avian cholera in the differential diagnoses during mortality events in Antarctica, even with the concurrent circulation of HPAIV.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Kappa-Flu, 101084171

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.16.694678v1?rss=1

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New {seasonal} #influenza {#H3N2} #variant is surging, but #vaccination still our best bet: #WHO (#UN, Dec. 17 '25)

 

16 December 2025 

Amid an early start to the Northern Hemisphere influenza season a new variant of the virus is rapidly gaining ground - but vaccination remains the “most effective defence”, the UN health agency said on Tuesday.

Influenza and other respiratory viruses are surging, Dr Wenqing Zhang, Unit Head for Global Respiratory Threats at the Department of Epidemic and Pandemic Threats Management of the World Health Organization (WHO) told reporters in Geneva, and this year is marked by “the emergence and the rapid expansion of a new AH3N2 virus subclade”.

The new variant - called J.2.4.1 or subclade K - was first noted in August in Australia and New Zealand and has since been detected in over 30 countries, she said.

“Current epidemiological data do not indicate an increase in disease severity, although this genetic shift makes a notable evolution in the virus,” Dr Zhang said.

Influenza viruses are constantly evolving, she explained, which is why the influenza vaccine composition is regularly updated.

“WHO tracks these changes, assesses associated risks to public health and makes vaccine composition recommendations twice a year, through a longstanding global system – the Global Influenza Surveillance and Response System (GISRS), in collaboration with other global experts,” Dr. Zhang said.

The new variant is not part of the composition of the latest vaccines produced for the Northern Hemisphere influenza season, the WHO expert explained.

Still, “early evidence suggests that current seasonal vaccines continue to offer protection against severe diseases and reduce the risk of hospital hospitalization,” she said.

WHO estimates that there are around one billion cases of seasonal influenza annually, including up to five million cases of severe respiratory illness. Up to 650 000 deaths each year are owing to seasonal influenza-related respiratory disease.

“Vaccination remains our most effective defence, including against drifted strains, particularly for high-risk populations and those taking care of them,” Dr Zhang insisted.

The WHO expert shared the results of an early estimation of the vaccine’s effectiveness against the new variant, published in the United Kingdom some weeks ago.

“It's quite promising,” she said, pointing to the data which showed that the vaccine is around 75 per cent effective against severe disease and hospitalization in children and around 35 per cent among adults.

Dr Zhang warned that the upcoming holiday season may bring a further surge in respiratory illnesses. “Advanced planning and preparedness efforts, including encouraging vaccination uptake and strengthening health system readiness, are strongly recommended,” she said.

The WHO expert advised countries to strengthen lab diagnostics and year‑round disease surveillance and to participate in the WHO GISRS surveillance network.

The network comprises influenza centres in 130 countries as well as a dozen reference laboratories.

Asked about whether the United States will remain a member of the network next year despite the country’s decision to leave WHO, effective 22 January 2026, Dr Zhang said that “from the flu perspective, from the respiratory surveillance and preparedness perspective, certainly we would need all the countries in the world to participate in the surveillance, preparedness and a response for influenza and other respiratory viruses because we don't know the next pandemic strain, when and where it would emerge”.

“And that time between the emergence and being picked up and characterized and put into vaccines…it would make a lot of difference with regards to the number of lives that could be saved,” she concluded.

Source: 

Link: https://news.un.org/en/story/2025/12/1166604

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Dynamics of B-cell response in #MERS-CoV #patients and survivors with hybrid #immunity

 

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutics are currently available. Understanding the immune response is critical for designing effective therapeutics. Here, we comprehensively characterized the dynamics of B-cell responses in severely infected MERS-CoV patients and survivors with SARS-CoV-2 exposure history. Infected patients developed robust neutralizing antibody responses within 1 month of illness, with moderate-to-high cross-neutralization activity against SARS-CoV-2. The enhanced neutralization activity coincided with an increased abundance of specific mutated, class-switched IgG clones. Notably, one such clone was detected at moderate prevalence in both patients, and its expansion was accompanied by high neutralization activity against both viruses. Conversely, MERS-CoV survivors demonstrated higher neutralization activity against MERS-CoV after vaccination, despite minimal changes in antibody titers and limited alterations in B-cell repertoire properties. This suggests that the enhanced neutralization activity may be mediated by the reactivation and expansion of cross-reactive memory B cells targeting conserved epitopes, originally generated in response to the virus that triggered the primary immune response. These findings provide valuable insights into the B-cell repertoire landscape during natural MERS-CoV infection and highlight the potential for identifying broadly neutralizing antibodies in individuals with hybrid immunity.

IMPORTANCE

This study examines the immune responses of MERS-CoV patients and survivors who have had confirmed exposure to SARS-CoV-2. It offers a unique opportunity to characterize cross-reactive B-cell responses in individuals possessing hybrid immunity to both pathogenic coronaviruses. To our knowledge, no previous studies have examined longitudinal changes in the B-cell repertoire in MERS-CoV patients or survivors before and after SARS-CoV-2 vaccination. Our findings reveal enhanced neutralization activity against both MERS-CoV and SARS-CoV-2 following infection or vaccination, which appears to be associated with distinct patterns of B-cell repertoire dynamics. Notably, the data strongly suggest the presence of potent cross-neutralizing antibody responses, particularly in MERS-CoV patients, driven by dominant B-cell clones. These results underscore the potential for identifying broadly neutralizing antibodies in individuals with hybrid immunity.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/mbio.03356-25?af=R

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#Poland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

A mute swan in Mazowieckie Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7123

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Chinese #Taipei - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

Samples from Qieding District, Kaohsiung City and Annan District, Tainan City were sent to the National Laboratory, Veterinary Research Institute (VRI), for diagnosis. Highly pathogenic avian influenza H5N1 subtype were confirmed by VRI. The sampling spots were disinfected. Surrounding poultry farms within 3 km radius of the sampling spot are under intensified surveillance for 28 days.

By Cp9asngf - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=27358997

A dead black-faced spoonbill (Platalea minor) was found in Sicao, Annan District, Tainan City. The specimen was sent to National Reference Laboratory for testing. It was confirmed as Highly Pathogenic Avian Influenza (HPAI) on December 7.

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By Photo by Laitche, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=46904763

A dead Eurasian Wigeon (Anas penelope) was found in Qieding District, Kaohsiung City. The specimen was sent to National Reference Laboratory for testing. It was confirmed as Highly Pathogenic Avian Influenza (HPAI) on December 3.

Source: 

Link: https://wahis.woah.org/#/in-review/7098

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#Global burden of lower respiratory #infections and aetiologies, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

 

Summary

Background

Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years.

Methods

Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years.

Findings

In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24–2·81) deaths and 98·7 million (87·7–112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4–47·4) since 2010, with a global mortality rate of 94·8 (75·6–116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000–721 000] deaths or 25·3% [24·5–26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000–298 000] deaths or 10·9% [10·3–11·3]), and Klebsiella pneumoniae (228 000 [204 000–261 000] deaths or 9·1% [8·8–9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000–201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900–75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths.

Interpretation

This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies—including newer interventions such as respiratory syncytial virus monoclonal antibodies—and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies.

Funding

Gates Foundation.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00689-9/abstract?rss=yes

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#Poland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

A wild Greylag Goose in Podlaskie Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7096

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#Namibia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

By MPF - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=102468449

Approximately 30 wild birds on an island near Lüderitz were observed exhibiting clinical signs consistent with highly pathogenic avian influenza (HPAI). Enhanced and continuous surveillance activities are ongoing to assess the extent of infection and monitor potential spread.

Source: 

Link: https://wahis.woah.org/#/in-review/7120

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The #potential of #H5N1 viruses to adapt to #bovine cells varies throughout #evolution

 

Abstract

Avian influenza H5N1 clade 2.3.4.4b viruses caused a global panzootic and, unexpectedly, widespread outbreaks in dairy cattle, therefore representing a pandemic threat. To inform control strategies, it is critical to determine whether the potential to adapt to bovine cells is a general feature of H5N1 viruses, is specific to viruses of clade 2.3.4.4b, or narrowly restricted to some genotypes within this clade. Using a large panel of recombinant viruses representing >60 years of H5N1 history and other IAVs for comparison, we demonstrate replicative fitness in bovine cells is: (i) highly variable across 2.3.4.4b genotypes, (ii) limited in viruses predating the global expansion of this clade, (iii) determined by the internal gene cassette, and (iv) not restricted to udder epithelial cells. Mutations in the PB2 polymerase subunit emerge as key determinants of adaptation, although their phenotypic effects are context dependent. Bovine B3.13 and some avian genotypes exhibit enhanced modulation of bovine interferon-induced antiviral responses, determined by at least PB2, nucleoprotein, and the non-structural protein NS1. Our results highlight the polygenic nature of IAV host range, and reveal that the replication fitness in bovine cells, and likely their potential to adapt to cattle, varies greatly during the evolutionary trajectory of H5N1 viruses.

Source: 

Link: https://www.nature.com/articles/s41467-025-67234-1

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