#Report of the 49th meeting of #WHO Global Advisory #Committee on #Vaccine #Safety 27–28 November 2025 (Excerpt, Mar. 6 '26)

 

{Excerpt}

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COVID-19 current vaccine safety status and insights 

-- Since 2021, GACVS has regularly reviewed the safety of COVID-19 vaccines, including through global pharmacovigilance data and dedicated reviews of myocarditis, pregnancy outcomes and other adverse events of special interest (AESI). 

-- The most recent updates reaffirmed that the benefits of vaccination outweigh the risks across all groups and advised continued monitoring for younger males and follow-up of persons who have reported vaccine-associated myocarditis. 

-- Many individuals have received three or more doses of COVID-19 vaccine. 

-- Some adverse events – such as myocarditis – seem to occur mainly after the second dose of mRNA COVID- 19 vaccines. 

-- However, the outcomes were less severe in persons who developed myocarditis after vaccination compared to those unvaccinated and following infections, including SARS- CoV-2. 

-- Also, children under six months of age seem to be at higher risk of severe COVID-19 infection along with people over the age of 65 years. 

-- WHO has recommended continued vaccination for high-priority groups while acknowledging that gaps remain in the evidence on the safety of repeated dosing, long-term outcomes, and in subgroups such as children and pregnant women. 

-- As of October 2025, for all COVID-19 vaccines, there were only 32 cases of perturbation of fetal development in EudraVigilance, of which most were reported with the original vaccine strains. 

-- An analysis of safety of protein-based COVID-19 vaccines by the Uppsala Monitoring Centre (UMC) showed that as of November 2025 there were almost 6 million reports for all COVID-19 vaccines in UMC’s VigiBase. 

-- Of these, 16 548 reports concerned updated COVID-19 vaccine variants; among these were 5085 reports for updated protein-subunit vaccines. 

-- Around 17.4% of these were serious, and 50 reported a fatal outcome. 

-- Most reports were for the variant NVX CoV 2373 and most deaths were older vaccinees aged 75 years or more. 

-- GACVS reviewed findings from the Scandinavian collaboration called SCOPE (Scandinavian studies of COvid-19 in PrEgnancy). 

-- Findings showed no increased risk of adverse pregnancy, maternal or neonatal outcomes after mRNA COVID-19 vaccination in pregnancy in Denmark, Norway and Sweden. 

-- As of September 2025, the recommendation for vaccination in pregnancy was revised to apply only to specific high-risk groups. 

-- A case-control study by SCOPE of all women with a miscarriage before 14 weeks and all women with a primary care-based confirmation of an ongoing pregnancy in the first trimester revealed no evidence of increased risk of early pregnancy loss after COVID-19 vaccination. 

-- A further investigation of COVID-19 infection and vaccination with mRNA vaccines during the first trimester of pregnancy and the risk of congenital anomalies, in a population-based cohort of 150 000 live-born infants in Denmark, Norway and Sweden, showed no increased risk of major congenital anomalies among infants whose mothers were vaccinated against COVID-19 during the first trimester. 

-- A SCOPE investigation of the association between COVID-19 vaccination and several pregnancy outcomes among a cohort of almost 160 000 singleton pregnancies between January 2021 and 2022 in Norway and Sweden showed that vaccination against COVID-19 during pregnancy was not associated with any of the studied adverse pregnancy outcomes. 

-- In another SCOPE study of COVID-19 vaccination during pregnancy and the risk of severe postpartum haemorrhage, including more than 300 000 single-term deliveries in Denmark, Norway and Sweden, no evidence was found of an association between COVID-19 vaccination at any time during pregnancy and severe postpartum hemorrhage. 

-- Finally, SCOPE investigated neonatal outcomes after COVID-19 vaccination with mRNA vaccine during pregnancy in a cohort of almost 200 000 infants in Norway and Sweden. 

-- Again, no increased odds were found of any adverse neonatal outcomes and neonatal mortality. 

-- In consideration of the evidence presented, GACVS members agreed the following: 

- Repeated-dose safety (including boosters with variant-containing vaccines): 

* Current evidence remains reassuring, with no new safety signals recently identified. 

- Safety of protein-based vaccines: 

* While generally well tolerated, reported adverse events include a proportion of serious individual case safety reports (ICSRs) in the global database. Several potential signals (e.g. tinnitus, antibody-dependent enhancement, thrombosis) require further evaluation. Additional data collection and analysis are therefore recommended to strengthen the evidence base for these vaccines. 

- Long-term outcomes of known risks (e.g. myocarditis, pregnancy outcomes): 

* Myocarditis continues to occur predominantly in younger adults, typically with mild-to- moderate severity and most frequently after the second dose. Longer follow-up studies are needed to define the long-term prognosis and risks of revaccination in affected individuals. 

- Subgroup-specific safety (children, young males, older adults, immunocompromised individuals, pregnant women): 

* Evidence to date shows no harmful effects of mRNA COVID-19 vaccination during pregnancy, including no increase in congenital anomalies, adverse perinatal outcomes, or some post-natal complications. Some studies even suggest lower odds of intracranial haemorrhage, cerebral ischaemia and neonatal mortality among infants of vaccinated mothers. 

- Safety monitoring during the transition to endemic COVID-19 vaccination: 

* Continued vigilance is required, particularly regarding more recent variant-adapted vaccines which remain safe on the basis of current data. Enhanced monitoring of protein-based vaccines is important given the comparatively limited evidence and the presence of identified risks that warrant further investigation.

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Source: 

Link: https://www.who.int/publications/journals/weekly-epidemiological-record

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#USA, #Wastewater Data for Avian #Influenza #H5 (CDC, Mar. 6 '26)

 

{Excerpt}

Time Period: February 22, 2026 - February 28, 2026

-- H5 Detection: 9 site(s) (2.0%)

-- No Detection: 443 site(s) (98.0%)

-- No samples in last week: 147 site(s)

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Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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#Montenegro - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

Backyard poultry in the Bijelo Polje Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7334

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Optimizing an avian #influenza #vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 #adjuvant

 

Abstract

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime–boost model. Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its potential as an adjuvant for next-generation influenza vaccines while underscoring the need for further optimization to achieve true cross-neutralizing protection.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709477v1

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#UK - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

{England, North Yorkshire}

22.7k commercial pheasant rearing premises. Samples taken were positive for HPAI H5N1. Birds presented clinical signs prior to testing.

Source: 

Link: https://wahis.woah.org/#/in-review/7337

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

 

Fourteen Coscoroba Swans in the Región de Valparaíso, Comuna Santo Domingo.

Source: 

Link: https://wahis.woah.org/#/in-review/7336

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Stabilization of the #H5 clade 2.3.4.4b #hemagglutinin improves #vaccine-elicited neutralizing #antibody responses in mice

 

Abstract

Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo–electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA–lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA–stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.

Source: 

Link: https://www.science.org/doi/10.1126/scitranslmed.aea8770

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#Dairy Sites with #Milk Exposure Are Most Likely to Have #Detection of #Influenza A Virus

 

Abstract

Highly pathogenic avian influenza virus of the H5N1 subtype has been infecting U.S. dairy cattle and spreading among dairy operations since March 2024. H5N1 surveillance systems for dairies are needed, but information on whether environmental sampling can inform these systems is lacking. To guide a surveillance framework, we determined the environmental sites with Influenza A virus (IAV) detection on H5N1-affected dairies (n = 25) in four states (California, Colorado, Michigan, and Ohio) and explored sample characteristics that may have influenced detection. A total of 581 samples from dairy environmental sites were characterized for IAV RNA via rRT-PCR, and classified into six categories. A total of 94 samples (16.2%) had IAV detected, and the Ct values measured from these samples were typically higher than those measured in bulk tank milk from a subset of sampled herds. A majority of IAV detections were made from the following site categories: milking equipment/personal protective equipment, parlor surfaces, and wastewater/lagoons/manure. These results suggest that environmental sites most likely to be contaminated with IAV on dairies are those with exposure to milk. Meanwhile, mixed effect logistic modeling showed that days into an outbreak that samples were collected was associated with IAV detection. These results provide a framework within which to continue the assessment of environmental sampling as a surveillance tool for dairy H5N1. This framework can be strengthened by studies that perform further IAV viral characterization and collect samples from sites prior to, during, and after H5N1 outbreak periods.

Source: 

Link: https://www.mdpi.com/2076-2607/14/3/584

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Evaluation of an #H5 #influenza virus #mRNA-lipid nanoparticle (LNP) #vaccine in lactating dairy #cows

 

Abstract

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.

Competing Interest Statement

S.E.H. and D.W. are co-inventors on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins and as a vaccine platform. D.W. is also named on patents describing the use of lipid nanoparticles and lipid compositions for nucleic acid delivery. S.E.H. reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. JDB consults for Apriori Bio, Invivyd, GSK, Pfizer, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to viral deep mutational scanning.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, 75N93021C00015

United States Department of Agriculture, https://ror.org/01na82s61, 5030-32000-231-000-D, 3200-231-112-I

United States Department of Energy, https://ror.org/01bj3aw27, DE-AC05-06OR23100

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709308v1

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#Pathogenesis of #H5N1 Clade 2.3.4.4b in dry Jersey #cows following intramammary inoculation shows within-host compartmentalization

 

Abstract

Dairy cattle have emerged as a prolific amplifying host for highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b and a new source for cross-species and zoonotic transmission. Independent introductions of H5N1 with unclear exposure routes have been reported in several dairy herds across the U.S. These events escalate the pandemic potential of HPAIV H5N1 as transmission within and between mammalian species present opportunities for mammalian adapted H5N1 viruses to emerge. Although more than 1000 herds have been infected, bovine H5N1 influenza virus pathogenesis, transmission, and evolution in dairy cattle remains not well characterized. Working with H5N1-infected lactating cattle in high containment has been a major challenge due to the required infrastructure and logistics associated with housing, husbandry, and waste management for this model. Thus, developing alternative bovine models that maintain biological relevance while reducing operational complexity is warranted. Here, we evaluate the susceptibility of lactating Jersey cattle in the dry-off period, and characterize the effect of inoculation dose on the mammary pathogenicity of HPAIV H5N1 genotype B3.13. The results of this study demonstrate that dairy cows 21 days into the dry-off period are highly susceptible to HPAIV H5N1, recapitulating the severe clinical and pathological outcomes observed in infected lactating cows under experimental conditions and in field cases. We also observed an association between virus dose and the onset and severity of mastitis in individual udder-quarters and compartmentalized clonal expansion of variant populations. Overall, this study demonstrates that dry cows can provide a feasible model to study H5N1 virology, pathology, and humoral immunology in dairy cows.

Competing Interest Statement

The J.A.R. laboratory received support from Tonix Pharmaceuticals, Genus plc, Xing Technologies and Zoetis outside of the reported work. J.A.R. is inventor on patents and patent applications, owned by Kansas State University, on the use of antivirals and vaccines for the treatment and prevention of virus infections. The other authors declare no competing interests.

Funder Information Declared

This work was supported by the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, the USDA Animal Plant Health Inspection Service’s NBAF Scientist Training Program, the AMP and MCB Cores of the Center on Emerging and Zoonotic Infectious Diseases (CEZID) , and the NIAID supported Centers of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016 and subcontract A21-0702-S001). NIGMS. The sequencing infrastructure used in the study was funded by the USDA Animal Plant Health Inspection Services (AP20VSD&B000C086), while sequencing methodology development was funded in part by the USDA National Institute of Food and Agriculture (NIFA) Agriculture and Food Research Initiative (AFRI) (award no. 2021-68014-33635). H.M.M. was supported in part by NIAID T32055397.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.04.709389v1

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#Panzootic #H5 #influenza viruses acquired #resistance to human head interface #antibodies

 

Abstract

Antibodies to the influenza hemagglutinin protein (HA) confer the strongest protection against infection. Immunity elicited by endemic, seasonal, human viruses is correlated with diminished disease severity and death caused by antigenically novel viruses. Antibodies to the HA head interface are broadly protective and abundant in human serologic and memory repertoires. Notably, few head interface antibodies from H5 naive donors are reported to bind H5 HAs. We find head interface antibodies engage a wide range of H5 isolates but fail to engage most isolates from the goose Guangdong (GsGd) lineage. We identify a single substitution, P221S, largely dictates antibody binding. Phylogenetic analysis indicates that P221S arose in a Chinese avian reservoir by the year 2000. Descendants of these viruses have caused the current global panzootic and have achieved sustained mammal-mammal transmission in farmed and wild mammals. Our findings demonstrate that viral evolution in non-mammalian species can, by chance, produce viruses that resist broadly protective human antibody responses.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014005

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#Statement of the 44th #Meeting of the #Polio #IHR #Emergency Committee (#WHO, summary)

 

{4 March 2026, excerpts}

The 44th meeting of the Emergency Committee under the International Health Regulations (IHR or Regulations) on the international spread of poliovirus was convened by the WHO Director-General on 14 January 2026 with eight out of nine Committee members and the adviser meeting via video conference with affected countries, supported by the WHO Secretariat. 

The Emergency Committee reviewed the latest epidemiological data on wild poliovirus type 1 (WPV1) and circulating vaccine-derived polioviruses (cVDPV) in the context of the global targets to interrupt endemic WPV1 transmission in 2026 and to stop cVDPV2 outbreaks by 2028 with subsequent certification of WPV1 eradication and cVDPV2 elimination. 

Technical updates were received about the situation in the following countries: 

- Afghanistan, 

- Angola, 

- Germany, 

- Lao People’s Democratic Republic, 

- Namibia, 

- Pakistan and 

- Papua New Guinea.

Amendments to the IHR, adopted by the Seventy-seventh World Health Assembly, through resolution WHA77.17 in June 2024, entered into force, generally, on 19 September 2025.

Key amendments to the IHR include, inter alia, broader poliovirus notification requirements; the introduction of the determination of “pandemic emergency” , a higher level of global public health alert with respect to a public health emergency of international concern (PHEIC); measures to strengthen equitable access to relevant health products; and recognition of health documents in non-digital and digital formats.

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Conclusion

The Committee unanimously concluded that the risk of international spread of polioviruses continues to constitute a Public Health Emergency of International Concern (PHEIC) and recommended extending the Temporary Recommendations for a further three months.

The Committee, after a thorough review of the epidemiological and programmatic situation, unanimously concluded that the event does not constitute a pandemic emergency.

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Source: 

Link: https://www.who.int/news/item/04-03-2026-statement-of-the-forty-fourth-meeting-of-the-polio-ihr-emergency-committee

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Mechanism of co-transcriptional cap snatching by #influenza #polymerase

 

Abstract

Influenza virus mRNAs are stable and competent for nuclear export and translation because they receive a 5′ cap(1) structure in a process called cap snatching1. During cap snatching, the viral RNA-dependent RNA polymerase (FluPol) binds to host RNA polymerase II (Pol II) and the emerging transcript2,3. The FluPol endonuclease then cleaves a capped RNA fragment that subsequently acts as a primer for the transcription of viral genes4,5. Here we present the cryogenic electron microscopy structure of FluPol bound to a transcribing Pol II in complex with the elongation factor DSIF in the pre-cleavage state. The structure shows that FluPol directly interacts with both Pol II and DSIF, positioning the FluPol endonuclease domain near the RNA exit channel of Pol II. These interactions are important for the endonuclease activity of FluPol and FluPol activity in cells. A second structure, trapped after cap snatching, shows that the cleaved capped RNA rearranges within FluPol, directing the capped RNA 3′ end toward the FluPol polymerase active site for viral transcription initiation. Together, our results provide the molecular mechanisms of co-transcriptional cap snatching by FluPol.

Source: 

Link: https://www.nature.com/articles/s41586-026-10189-0

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#India - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

A poultry farm in Bihar State.

Source: 

Link: https://wahis.woah.org/#/in-review/7319

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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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Fatal #human #H3N8 #influenza virus has a moderate #pandemic #risk

 

Abstract

In China, low pathogenic avian influenza (LPAI) H3N8 virus is widespread among chickens and has recently caused three zoonotic infections, with the last one in 2023 being fatal. Here we evaluated the relative pandemic risk of this 2023 zoonotic H3N8 influenza virus, utilizing our previously published decision tree. Serological analysis indicated that a large proportion of the human population does not have any cross-neutralizing antibodies against this H3N8 strain. LPAI H3N8 displayed a dual affinity for α2–3 and α2–6 sialic acids and replicated efficiently in human bronchial epithelial cells. Furthermore, we observed H3N8 transmission via direct contact but not aerosols to ferrets with pre-existing H3N2 immunity. Although pre-existing H3N2 immunity resulted in a shortened disease course in ferrets, it did not reduce disease severity or replication in the respiratory tract. This study suggests that this zoonotic H3N8 strain has moderate pandemic potential and emphasizes the continued need for avian influenza surveillance.

Author summary

Low pathogenic avian influenza (LPAI) viruses circulate widely amongst birds and are a major public health concern for their ability to cross over to other species, including humans. Here we characterize the pandemic potential of an H3N8 LPAI virus that caused a lethal human infection. While this strain was only able to transmit by direct contact, we found that it did exhibit some human adaptations, and pre-existing immunity did not reduce replication or pathogenesis, suggesting that it is a moderate pandemic risk and needs to be monitored given the potential public health threat.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013586

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Potent efficacy of an NA-targeting #antibody against a broad spectrum of #H5N1 #influenza viruses

 

Abstract

For nearly 30 years, Goose/Guangdong-derived highly pathogenic avian influenza H5N1 viruses have posed significant risks to economic stability, food security, and public health. Virus evolution has resulted in various clades, including the panzootic subclade 2.3.4.4b, recognized for its pandemic potential. Here we present the potent in vitro activity of FNI9, a pan-influenza NA-inhibiting monoclonal antibody, against a range of pseudoparticles with NA spanning decades of H5N1 virus evolution. FNI9 also shows strong prophylactic protection in female mice against lethal challenges with H5N1 from clade 1 and 2.3.4.4b. Cryo-EM and molecular dynamics analysis reveal that FNI9 binds to 7 highly conserved H5N1 NA residues (R118, E119, D151, E228, E278, R293, and R368). In silico evolutionary escape profiling and machine learning predict low escapability, high fitness costs, and minimal spread likelihood for viral mutations that evade FNI9 binding. These findings support FNI9 broad protection and underscore the NA role in future influenza vaccine design.

Source: 

Link: https://www.nature.com/articles/s41467-026-70036-8

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#Vietnam - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

Backyard poultry in Hà Tĩnh and Đắk Lắk Regions.

Source: 

Link: https://wahis.woah.org/#/in-review/7272

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Guernica, Pablo Picasso (1937, murales inspired by the original work)

 

Di Papamanila - Fotografia autoprodotta, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9469068

Source: 

Link: https://it.wikipedia.org/wiki/Guernica_(Picasso)

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Unveiling the #epitope #repertoires and protective roles of #MERS-CoV-specific T cells in mice

 

Highlights

• MERS-CoV structural proteins and ORFs potently induce T cell responses in mice

• MERS-CoV-specific T cell epitope repertoires are identified in C57BL/6 and BALB/c mice

• Airway ORF4b208-CD4+ and ORF5167-CD8+ T cells are optimal effector T cells

• ORF4b208 and ORF5167-specific T cells protect mice against MERS-CoV infection

Summary

Since its initial emergence in 2012, MERS-CoV has remained endemic and a global health threat. While accessory proteins (ORFs) are known for immune evasion, their role in adaptive immunity is unexplored. This study systematically investigated T cell responses against MERS-CoV ORFs. We mapped epitope repertoires targeting structural proteins and ORFs in C57BL/6 and BALB/c mice, revealing that ORFs potently induced virus-specific T cells. Notably, ORF5 induced the dominant CD8+ T cell responses in BALB/c mice. Further analysis revealed that ORF4b208-specific CD4+ and ORF5167-specific CD8+ T cells in the respiratory tract exhibited polyfunctional cytokine profiles, high antigen sensitivity, and potent in vivo cytotoxicity. These specific T cells played protective roles during MERS-CoV infection by promoting viral clearance. Collectively, this study identified MERS-CoV-specific T cell epitopes and elucidated the roles of ORF4b- and ORF5-specific T cells, enhancing our understanding of anti-MERS-CoV T cell responses and advancing vaccine design strategies against MERS-CoV.

Source: 

Link: https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00121-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472600121X%3Fshowall%3Dtrue

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