Avian #Influenza Virus #Infections in #Felines: A Systematic Review of Two Decades of Literature

Abstract

As an avian influenza virus (AIV) panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern. Domestic cats are susceptible to AIV infection and provide a potential pathway for zoonotic spillover to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of AIV infections in felines reported from 2004 – 2024. We identified 607 AIV infections in felines, including 302 associated deaths, comprising 18 countries and 12 felid species. We observed a drastic flux in the number of AIV infections among domestic cats in 2023 and 2024, commensurate with the emergence of H5N1 clade 2.3.4.4b. We estimate that this phenomenon is underreported in the scientific literature and argue that increased surveillance among domestic cats is urgently needed.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.04.30.24306585v2

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Highly Pathogenic Avian #Influenza A(#H5N1) Virus: Interim #Recommendations for #Prevention, #Monitoring, and Public Health #Investigations

{Summary as of December 26 '24}

What to know

-- This guidance outlines CDC’s recommendations for preventing human exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses and infection prevention and control measures, including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons, and antiviral chemoprophylaxis of exposed persons.

Summary

The purpose of this guidance is to outline CDC's recommendations for preventing exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses, infection prevention and control measures including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus), and antiviral chemoprophylaxis of exposed persons. These recommendations are based on available information and will be updated as needed when new information becomes available.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html

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#Genetic #Sequences of Highly Pathogenic Avian #Influenza A(#H5N1) Viruses Identified in a Person in #Louisiana

What to know

-- CDC has sequenced the influenza viruses in specimens collected from the patient in Louisiana who was infected with, and became severely ill from HPAI A(H5N1) virus. 

-- The genomic sequences were compared to other HPAI A(H5N1) sequences from dairy cows, wild birds and poultry, as well as previous human cases and were identified as the D1.1 genotype. 

-- The analysis identified low frequency mutations in the hemagglutinin gene of a sample sequenced from the patient, which were not found in virus sequences from poultry samples collected on the patient’s property, suggesting the changes emerged in the patient after infection.

Background

This is a technical summary of an analysis of the genomic sequences of the viruses identified in two upper respiratory tract specimens from the patient who was severely ill from an infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus in Louisiana. 

The patient was infected with A(H5N1) virus of the D1.1 genotype virus that is closely related to other D1.1 viruses recently detected in wild birds and poultry in the United States and in recent human cases in British Columbia, Canada, and Washington State. 

This avian influenza A(H5N1) virus genotype is different from the B3.13 genotype spreading widely and causing outbreaks in dairy cows, poultry, and other animals, with sporadic human cases in the United States. 

Deep sequencing of the genetic sequences from two clinical specimens from the patient in Louisiana was performed to look for changes associated with adaptation to mammals. 

There were some low frequency changes in the hemagglutinin (HA) gene segment of one of the specimens that are rare in people but have been reported in previous cases of A(H5N1) in other countries and most often during severe infections. 

One of the changes found was also identified in a specimen collected from the human case with severe illness detected in British Columbia, Canada, suggesting they emerged during the clinical course as the virus replicated in the patient. 

Analysis of the N1 neuraminidase (NA), matrix (M) and polymerase acid (PA) genes from the specimens showed no changes associated with known or suspected markers of reduced susceptibility to antiviral drugs.

CDC Update

December 26, 2024 – CDC has sequenced the HPAI A(H5N1) avian influenza viruses in two respiratory specimens collected from the patient in Louisiana who was severely ill from an A(H5N1) virus infection. 

CDC received two specimens collected at the same time from the patient while they were hospitalized for severe respiratory illness: a nasopharyngeal (NP) and combined NP/oropharyngeal (OP) swab specimens. 

Initial attempts to sequence the virus from the patient's clinical respiratory specimens using standard RNA extraction and multisegment-RTPCR (M-RTPCR)1 techniques yielded only partial genomic data and virus isolation was not successful. 

Nucleic acid enrichment was needed to sequence complete genomes with sufficient coverage depth to meet quality thresholds. 

CDC compared the influenza gene segments from each specimen with A(H5N1) virus sequences from dairy cows, wild birds, poultry and other human cases in the U.S. and Canada. 

The genomes of the virus (A/Louisiana/12/2024) from each clinical specimen are publicly posted in GISAID (EPI_ISL_19634827 and EPI_ISL_19634828) and GenBank (PQ809549-PQ809564).

Summary of amino acid mixtures identified in the hemagglutinin (HA) of clinical specimens from the patient.

Overall, the hemagglutinin (HA) sequences from the two clinical specimens were closely related to HA sequences detected in other D1.1 genotype viruses, including viruses sequenced from samples collected in November and December 2024 in wild birds and poultry in Louisiana. 

The HA genes of these viruses also were closely related to the A/Ezo red fox/Hokkaido/1/2022 candidate vaccine virus (CVV) with 2 or 3 amino acid changes detected. 

These viruses have, on average, 3 or 4 amino acid changes in the HA when compared directly to the A/Astrakhan/3212/2020 CVV sequence. 

These data indicate the viruses detected in respiratory specimens from this patient are closely related to existing HPAI A(H5N1) CVVs that are already available to manufacturers, and which could be used to make vaccines if needed.

There were some differences detected between the NP/OP and the NP specimens. 

Despite the very close similarity of the D1.1 sequences from the Louisiana human case to bird viruses, deep sequence analysis of the HA gene segment from the combined NP/OP sample detected low frequency mixed nucleotides corresponding to notable amino acid residues (using mature HA sequence numbering):

-- A134A/V [Alanine 88%, Valine 12%];

- N182N/K [Asparagine 65%, Lysine 35%]; and

- E186E/D [Glutamic acid 92%, Aspartic Acid 8%].

The NP specimen, notably, did not have these low frequency changes indicating they may have been detected from swabbing the oropharyngeal cavity of the patient. 

While these low frequency changes are rare in humans, they have been reported in previous cases of A(H5N1) in other countries and most often during severe disease2345. 

The E186E/D mixture, for example, was also identified in a specimen collected from the severe human case detected in British Columbia, Canada67.

This summary analysis focuses on mixed nucleotide detections at residues A134V, N182K, E186D as these changes may result in increased virus binding to α2-6 cell receptors found in the upper respiratory tract of humans. 

It is important to note that these changes represent a small proportion of the total virus population identified in the sample analyzed (i.e., the virus still maintains a majority of 'avian' amino acids at the residues associated with receptor binding). 

The changes observed were likely generated by replication of this virus in the patient with advanced disease rather than primarily transmitted at the time of infection. 

Comparison of influenza A(H5) sequence data from viruses identified in wild birds and poultry in Louisiana, including poultry identified on the property of the patient, and other regions of the United States did not identify these changes. 

Of note, virus sequences from poultry sampled on the patient's property were nearly identical to the virus sequences from the patient but did not have the mixed nucleotides identified in the patient's clinical sample, strongly suggesting that the changes emerged during infection as virus replicated in the patient. 

Although concerning, and a reminder that A(H5N1) viruses can develop changes during the clinical course of a human infection, these changes would be more concerning if found in animal hosts or in early stages of infection (e.g., within a few days of symptom onset) when these changes might be more likely to facilitate spread to close contacts. 

Notably, in this case, no transmission from the patient in Louisiana to other persons has been identified. 

The Louisiana Department of Public Health and CDC are collaborating to generate additional sequence data from sequential patient specimens to facilitate further genetic and virologic analysis.

Additional genomic analysis

The genetic sequences of the A(H5N1) viruses from the patient in Louisiana did not have the PB2 E627K change or other changes in polymerase genes associated with adaptation to mammals and no evidence of low frequency changes at critical positions. 

And, like other D1.1 genotype viruses found in birds, the sequences lack PB2 M631L, which is associated with viral adaptation to mammalian hosts, and which has been detected in >99% of dairy cow sequences but is only sporadically found in birds. 

Analysis of the N1 neuraminidase (NA), matrix (M) and polymerase acid (PA) genes from the specimens showed no changes associated with known or suspected markers of reduced susceptibility to antiviral drugs. 

The remainder of the genetic sequences of A/Louisiana/12/2024 were closely related to sequences detected in wild bird and poultry D1.1 genotype viruses, including poultry identified on the property of the patient, providing further evidence that the human case was most likely infected following exposure to birds infected with D1.1 genotype virus.

Follow Up Actions

Overall, CDC considers the risk to the general public associated with the ongoing U.S. HPAI A(H5N1) outbreak has not changed and remains low. 

The detection of a severe human case with genetic changes in a clinical specimen underscores the importance of ongoing genomic surveillance in people and animals, containment of avian influenza A(H5) outbreaks in dairy cattle and poultry, and prevention measures among people with exposure to infected animals or environments.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-12232024.html

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Recurring #incursions and #dissemination of novel #Eurasian-origin #H5Nx avian #influenza viruses in Atlantic #Canada

Abstract

Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards. This lineage has evolved and diversified over time, with a recent important derivative being the 2.3.4.4b sub-lineage, which has caused significant mortality events in wild bird populations. An H5N1 clade 2.3.4.4b virus was transmitted into North America from Eurasia in 2021, with the first detection being in Newfoundland and Labrador in Atlantic Canada, and this virus and its reassortants then spread broadly throughout North America and beyond. Following the first 2021 detection, there have been three additional known incursions of Eurasian-origin strains into Atlantic Canada, a second H5N1 strain in 2022 and two H5N5 strains in 2023. In this study, we document a fifth incursion in Atlantic Canada that occurred in 2023 by another H5N5 strain. This strain spread throughout Atlantic Canada and into Quebec, infecting numerous species of wild birds and mammals. Genomic analysis revealed mammalian-adaptive mutations in some of the detected viruses (PB2-E627K and PB2-D701N) and mutations in the hemagglutinin (HA) and neuraminidase (NA) genes that are associated with enhanced viral fitness and avian transmission capabilities. Our findings indicate that this virus is continuing to circulate in wildlife, and confirms Atlantic Canada is an important North American entry point for Eurasian IAVs. Continued surveillance and genomic analysis of IAVs detected in the region is crucial to monitor the evolution of these viruses and assess potential risks to wildlife and public health.

Source: Virus Evolution, https://academic.oup.com/ve/article/10/1/veae111/7926332

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Introducing a #framework for within-host dynamics and #mutations modelling of #H5N1 #influenza #infection in #humans

Abstract

Avian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility, possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For three mutations, we found a peak probability of approximately 10-3 that a human case of H5N1 influenza produces at least one virion during the infectious period. Our findings provide insights into the risk of differing infectious pathways of influenza A(H5N1) (namely avian-human vs avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.09.01.24312235v2

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#Detection and #Phylogenetic Characterization of #Influenza D in Swedish #Cattle

Abstract

Increased evidence suggests that cattle are the primary host of Influenza D virus (IDV) and may contribute to respiratory disease in this species. The aim of this study was to detect and characterise IDV in the Swedish cattle population using archived respiratory samples. This retrospective study comprised a collection of a total 1763 samples collected between 1 January 2021 and 30 June 2024. The samples were screened for IDV and other respiratory pathogens using real-time reverse transcription quantitative PCR (rRT-qPCR). Fifty-one IDV-positive samples were identified, with a mean cycle threshold (Ct) value of 27 (range: 15–37). Individual samples with a Ct value of <30 for IDV RNA were further analysed by deep sequencing. Phylogenetic analysis was performed by the maximum likelihood estimation method on the whole IDV genome sequence from 16 samples. The IDV strains collected in 2021 (n = 7) belonged to the D/OK clade, whereas samples from 2023 (n = 4) and 2024 (n = 5) consisted of reassortants between the D/OK and D/660 clades, for the PB2 gene. This study reports the first detection of IDV in Swedish cattle and the circulation of D/OK and reassortant D/OK-D/660 in this population.

Source: Viruses, https://www.mdpi.com/1999-4915/17/1/17

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#USA, #Birdflu tightens grip on #California as #human cases rise

 {Excerpts}

SACRAMENTO, the United States -- California's battle against avian influenza A (H5N1) intensified amid spreading infections across dairy farms and a growing number of human infection, including two newly confirmed cases in Stanislaus and Los Angeles counties.

The virus, commonly known as bird flu, has infected 659 of California's 984 dairy operations since August, with one-quarter of these cases emerging in the past month alone, according to California authorities.

The rapid spread through the state's dairy industry prompted Governor Gavin Newsom to declare a state of emergency last week to protect agricultural workers and public health.

(...)

The outbreak's human impact has grown increasingly severe, with California reporting at least 36 confirmed cases -- more than half of the nation's total of 65, according to the latest report by the U.S. Centers for Disease Control (CDC) on Tuesday, though the actual count is likely higher as recent local confirmations may not yet be reflected in federal data.

Two new cases were confirmed Monday in California's Los Angeles County and Stanislaus County. Both individuals were exposed to livestock infected with bird flu at a worksite, and both had mild symptoms and were treated with antiviral medications, according to the two counties' health departments.

Public health officials have been monitoring wastewater across the state, detecting the virus in several Bay Area locations, including San Francisco, Napa, and San José. However, California State Epidemiologist Erica Pan explained to ABC30 that these detections might be primarily due to "residential or other commercial milk dumping down in the sinks."

Although health officials said the risk remains low for the general public, the virus kills 90 percent to 100 percent of infected poultry and about 1 percent to 2 percent of cows. California State Veterinarian Annette M. Jones noted that infected cows may never fully recover.

As the country's largest dairy producing state, California faced a heavy economic toll from the bird flu outbreak. The virus has led to quarantines and increased testing requirements. The authorities said the state is now testing its 1.7 million cows weekly.

California's milk production dropped 9.2 percent in November from the same month last year, the most significant decline recorded, according to the monthly Milk Production Report released by the U.S. Department of Agriculture (USDA) on Dec. 19. Meanwhile, California's reduced output has led to a 1 percent decrease in national milk production, raising concerns over U.S. dairy product availability and costs.

The state's poultry operations have also been hit hard. The California Department of Food and Agriculture reported that 51 commercial poultry operations and nine backyard flocks across the state had been affected.

The virus has also appeared in unexpected places, with Los Angeles County confirming two cases in domestic cats that consumed contaminated raw milk.

(...)

Source: China Daily, https://www.chinadaily.com.cn/a/202412/26/WS676cb951a310f1265a1d503b.html

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#USA, #Oregon: Morasch #Meats of #Portland Voluntary #Recall of Northwest Naturals Brand 2lb #Feline #Turkey Recipe Raw & Frozen #Pet #Food Due to #HPAI {#H5N1} Contamination

The Oregon Department of Agriculture (ODA) is alerting pet owners that samples of Northwest Naturals brand 2lb Turkey Recipe raw & frozen pet food tested positive for a H5N1 strain of the Highly Pathogenic Avian Influenza (HPAI) virus. 

Testing conducted by the U.S. Department of Agriculture’s (USDA) National Veterinary Services Laboratories (NVSL) and the Oregon Veterinary Diagnostic Laboratory (ODVL) at Oregon State University confirmed a house cat in Washington County contracted H5N1 and died after consuming the raw frozen pet food. 

Tests confirmed a genetic match between the virus in the raw and frozen pet food and the infected cat.

“We are confident that this cat contracted H5N1 by eating the Northwest Naturals raw and frozen pet food,” said ODA State Veterinarian Dr. Ryan Scholz. 

“This cat was strictly an indoor cat; it was not exposed to the virus in its environment, and results from the genome sequencing confirmed that the virus recovered from the raw pet food and infected cat were exact matches to each other.”

Northwest Naturals, a Portland, Oregon-based company, is voluntarily recalling its Northwest Naturals brand 2lb Feline Turkey Recipe raw & frozen pet food. 

The recalled product is packaged in 2-pound plastic bags with “Best if used by” dates of 05/21/26 B10 and 06/23/2026 B1. 

The product was sold nationwide through distributors in AZ, CA, CO, FL, GA, IL, MD, MI, MN, PA, RI and WA in the United States, and British Columbia in Canada. 

Customers who have purchased the recalled product should immediately discard the product and contract the place of purchase for a full refund. 

For additional information or questions, customers may contact Northwest Naturals of Portland at info@nw-naturals.net or 866-637-1872 from 7:00 AM to 3:30 PM PST, Monday through Friday

The Oregon Health Authority (OHA) and local public health officials are monitoring household members who had contact with the cat for flu symptoms. 

To date, no human cases of HPAI have been linked to this incident, and the risk of HPAI transmission to humans remains low in Oregon. 

Since 2022, OHA has partnered with ODA through a One Health approach to investigate human exposures to animal outbreaks of avian influenza.

To avoid the spread of disease, including HPAI, state, and federal experts strongly encourage people and their pets to:

-- Avoid consuming raw or undercooked meat products

-- Avoid consuming raw dairy

-- Limit contact with sick or dead animals

-- Wash your hands after handling raw animal products or contact with sick/dead animals

-- Report sick or dead birds to ODA at 503-986-4711

-- Keep pets or poultry away from wild waterfowl

This case reminds us that feeding raw meat products to pets or consuming them yourself can lead to severe illness. 

Raw meat may contain harmful pathogens, including Salmonella, Listeria, E. coli, and H5N1. These pathogens are destroyed when meat is thoroughly cooked. 

Raw milk, which has not been pasteurized, can also carry harmful germs. Pasteurization of milk eliminates disease-causing pathogens, including HPAI.

Although Oregon has reported one confirmed human case of HPAI, there are no confirmed cases of the virus in dairy cows or cow milk. 

As a precautionary measure, ODA announced on December 11 that it will test milk from every commercial dairy across the state. Neighboring states such as Idaho, Nevada, and California have reported HPAI cases in dairy cattle herds, contributing to over 700 confirmed cases in 16 states nationwide.

Source: Department of Agriculture, https://apps.oregon.gov/oregon-newsroom/OR/ODA/Posts/Post/morasch-meats-voluntary-recall-feline-raw-pet-food-hpai

#Mpox #mRNA-1769 #vaccine inhibits #orthopoxvirus #replication at intranasal, intrarectal, and cutaneous sites of inoculation

Abstract

We previously reported that mice immunized twice with a lipid nanoparticle vaccine comprising four monkeypox viral mRNAs raised neutralizing antibodies and antigen-specific T cells and were protected against a lethal intranasal challenge with vaccinia virus (VACV). Here we demonstrated that the mRNA vaccine also protects mice against intranasal and intraperitoneal infections with monkeypox virus and bioluminescence imaging showed that vaccination greatly reduces or prevents VACV replication and spread from intranasal, rectal, and dermal inoculation sites. A single vaccination provided considerable protection that was enhanced by boosting for at least 4 months. Protection was related to the amount of mRNA inoculated, which correlated with neutralizing antibody levels. Furthermore, immunocompetent and immunodeficient mice lacking mature B and T cells that received serum from mRNA-immunized macaques before or after VACV challenge were protected. These findings provide insights into the mechanism and extent of mRNA vaccine-induced protection of orthopoxviruses and support clinical testing.

Source: npj Vaccines, https://www.nature.com/articles/s41541-024-01052-2

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#Recommendations for the #surveillance of #influenza A(#H5N1) in #cattle

Summary 

Beyond domestic poultry, influenza A(H5N1) of clade 2.3.4.4b has spread to almost all regions, infecting a wide range of wild birds, marine and terrestrial mammals, and recently, cattle in the United States of America. When an influenza virus is circulating in both avian and mammalian populations, the likelihood of spillover to humans and risk to public health may increase. The reported events of the influenza A(H5N1) virus among terrestrial and marine mammals in several countries, including the recent cases detected in the United States of America, have made it necessary to improve virus detection in cattle and other susceptible mammals and closely monitor virus evolution and adaptation to extraordinary hosts. These recommendations aim to support countries in planning surveillance for influenza A(H5N1) in cattle to enhance early detection, to generate evidence-based information to mitigate the impacts of spillover from birds to cattle, and to prevent transmission between cattle herds. Additionally, these recommendations aim to assist countries, especially low- and middle-income countries, in optimizing the use of limited resources to achieve their surveillance objectives through leveraging existing surveillance programmes. The Food and Agriculture Organization of the United Nations (FAO) recommends that all countries maintain passive surveillance for A(H5N1) to rapidly detect spillover events in non-avian species, using an appropriate case definition alongside education and outreach to relevant stakeholders to improve awareness of this emerging disease. Additionally, countries may choose to use other surveillance approaches to leverage routine and opportunistic sampling to evaluate the health of cattle populations. Event-based surveillance may also be a helpful tool in early detection. For at-risk countries,1 targeted or risk-based surveillance approaches can be used to more closely assess cattle health at the interface with poultry or wild birds, investigate suspected outbreaks in cattle, and demonstrate freedom from infection. These recommendations have a broad application to other susceptible farmed mammals.

(...)

Source: FAO, https://openknowledge.fao.org/items/4c29fcb1-67e2-4a37-a780-cb4fe0c9f253

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#USA, #California: Public #Health Confirms #Human #H5 #Birdflu Case in #LA County

 {Excerpt}

{December 23 '24}

The Los Angeles County Department of Public Health has confirmed a human case of H5 bird flu in an adult who was exposed to livestock infected with H5 Bird flu at a worksite. 

This is the first human case of H5 bird flu detected in LA County. 

The person had mild symptoms, has been treated with antivirals, and is recovering at home. 

The overall risk of H5 bird flu to the public remains low.

There is currently no evidence of person to person spread of this virus. 

Close contacts of the infected person and other workers exposed at the worksite are being monitored for symptoms and have been offered personal protective equipment, testing and antiviral prophylaxis. 

No additional cases have been identified at this time. 

Public Health is working closely with the Centers for Disease Control and Prevention (CDC) and the California Department of Public Health (CDPH) on the ongoing investigation.

“People rarely get bird flu, but those who interact​ with infected livestock or wildlife ​have a greater risk of infection. This case reminds us to take basic precautions to prevent being exposed,” said Muntu Davis, MD, MPH, Los Angeles County Health Officer. 

“People should avoid unprotected contact with sick or dead animals including cows, poultry, and wild birds; avoid consuming raw or undercooked animal products, such as raw milk; and protect pets and backyard poultry from exposure to wild animals. It is also important for everyone to get the seasonal flu vaccine, which can help prevent severe seasonal flu illness and lower the risk of getting both seasonal and bird flu infections at the same time if exposed.”

(...)

Source: Los Angeles County Public Health Department, http://publichealth.lacounty.gov/phcommon/public/media/mediapubHPdetail.cfm?cur=cur&prid=4915&row=25&start=1

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Natural #infection of common #cranes (Grus grus) with highly pathogenic avian #influenza #H5N1 in #Serbia

{Abstract}

Introduction: 

The late autumn epizootic of the highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in Serbia in 2023 caused massive mortality in the migratory population of common cranes (Grus Grus). This is the first time HPAIV has been identified in the common crane in Serbia, leading to mass mortality of this bird species.

Methods: 

To understand the pathological impact of HPAIV in cranes, we evaluated the pathological changes in the tissues of common cranes. Additionally, we report genomic characterization of HPAI/H5N1. In total, 14 juvenile common crane carcasses were examined.

Results: 

Infected birds primarily exhibited neurologic signs, including ataxia and incoordination. Grossly, necrotizing pancreatitis was the most common finding, while microscopic lesions included necrosis, inflammation and hemorrhages in the lungs, spleen, brain, liver and kidneys. Based on RT-PCR, all birds were infected with the HPAI H5N1 virus, as viral RNA was detected in all 14 selected tissues. Genetic analysis revealed that our H5N1 isolate could be grouped with highly pathogenic avian influenza clade 2.3.4.4b, subgroup DA, and is very closely related to the H5N1 strains isolated from the common crane and turkey from Croatia, the common crane from Italy and the Ural owl from Slovakia.

Discussion: 

Our findings showed that common cranes are highly susceptible to natural infection with the HPAI H5N1 virus of clade 2.3.4.4b and may serve as bio-sentinels for the presence of the HPAI virus in wildlife.

Source: Frontiers of Veterinary Science, https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1462546/full

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#USA, #California: Current #H5N1 #Birdflu #Situation in #Humans {1 new case, total now = 37}

 {Excerpt, edited}

Updated December 23, 2024​

-- ​​​The current risk to the public remains low.  ​​

-- No person-to-person spread of bird flu has been detected in California. 

-- People rarely get bird flu, but those who interact​ with infected dairy cows, poultry, or wildlife ​have a greater risk of infection.​​

-- Pasteurized milk and dairy products are safe to consume. Pasteurization inactivates the bird flu virus.​​

-- CDPH is working to protect public health related to bird flu. We monitor infection data, evolving science, and the people affected. Our knowledge will change as we learn more. We are committed to reducing the impact to those at highest risk.

Human Cases in Califo​rnia​

​​​​​​​Confirmed Human Cases​: 37 {+1}

​These numbers were last updated on December 23, 2024.

California has 1 additional probable case with dairy cow exposure that meets the  Council of State and Territorial Epidemiologists (CSTE) ​probable case definition (PDF)​. That case tested positive by a local lab and confirmatory testing at CDC was negative.​​

Confirmed human case summary during the 2024 outbreak, by exposure source.

-- ​Cattle: ​36

-- Poultry:​ 0

-- ​Unkn​own: ​1

--- ​Total: ​37

(...)

Source: Department of Health, https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/Bird-Flu.aspx

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Targets of #influenza #human T-cell response are mostly conserved in #H5N1

ABSTRACT

Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis of epitope data curated in the Immune Epitope Database (IEDB). We found that the patterns of immunodominance of seasonal influenza viruses circulating in humans and H5N1 are similar. We further conclude that a significant fraction of the T-cell epitopes is conserved at a level associated with cross-reactivity between avian and seasonal sequences, and we further experimentally demonstrate extensive cross-reactivity in the most dominant T-cell epitopes curated in the IEDB. Based on these observations, and the overall similarity of the neuraminidase (NA) N1 subtype encoded in both HPAI and seasonal H1N1 influenza virus as well as cross-reactive group 1 HA stalk-reactive antibodies, we expect that a degree of pre-existing immunity is present in the general human population that could blunt the severity of human H5N1 infections. 

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.03479-24

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Avian #influenza: past, present and future

Summary 

Avian influenza is not a new disease, but the emergence of high pathogenicity avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/96 lineage (Gs/GD) has necessitated fundamental changes to prevention and control strategies for this disease. No longer just an avian disease, avian influenza is capable of causing severe disease in humans and is considered a potential human pandemic threat requiring One Health approaches. In addition, Gs/GD HPAI viruses have developed the capacity to be carried across and between continents by migratory birds. Given the persistence of the current A(H5N1) clade 2.3.4.4b viruses in wild birds, enhanced measures to prevent and control infection will be needed. In most countries, infection in poultry can be eliminated, although questions will remain about the sustainability of repeated stamping out. Systematic preventive vaccination should be seriously considered as a method for reducing the number of outbreaks. HPAI will not be eliminated from countries where Gs/GD viruses remain enzootic until major changes are made to the way that poultry are reared and sold, vaccination is improved and other factors that inhibit reporting and response are overcome. Currently, focus lies on Gs/GD HPAI, yet control of low pathogenicity avian influenza viruses also requires attention, including the development of vaccines that are appropriately matched to circulating strains of virus.

Source: WOAH, https://doc.woah.org/dyn/portal/index.xhtml?page=alo&aloId=44447

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Strategic #challenges in the global #control of high pathogenicity avian #influenza

Summary 

H5Nx A/Goose/Guangdong/1/96 Eurasian lineage high pathogenicity avian influenza (HPAI) viruses have been the main HPAI strains detected globally since 2005. These have spread around the world, causing a panzootic that has spanned six continents, with continual threat to not only wild and captive birds and poultry, but also wild, captive and domestic mammals and humans. The viruses’ ecology and epidemiology – especially the 2.3.4.4b clade – have changed, with over 489 species of birds infected and spreading the virus over migratory routes. This results in the death of many birds, including endangered species, and serves as a source of transmission to poultry and mammals. Improved surveillance and sharing of HPAI virus sequences, metadata and viruses across the veterinary, public health, wildlife and environment sectors are needed to elucidate the population dynamics of the infections, which is crucial to addressing this complex One Health issue. The development of appropriate mitigation strategies or changes in husbandry, production and selling practices can reduce the risk of viruses being introduced into farms, as well as their amplification and viral evolution, and any spill-back to wild birds. Approaches to prevention and control of HPAI in countries where these 2.3.4.4b viruses remain entrenched in poultry, or places at risk of virus introduction via wild bird populations, involve measures to reduce the effects of the disease in poultry (including enhanced farm bio- security, vaccination, zoning and compartmentalisation). Their uptake reflects the difficulties encountered in relying solely on biosecurity for disease prevention and on stamping out alone for virus control and elimination. The World Organisation for Animal Health’s Terrestrial Animal Health Code allows use of vaccination of poultry under specific conditions and without negatively impacting HPAI-free status if appropriate surveillance is conducted, thus supporting safe trade in poultry and poultry products. Nevertheless, concerns regarding loss of valuable export markets still interfere with greater utilisation of vaccination.

Source: WOAH, https://doc.woah.org/dyn/portal/index.xhtml?page=alo&aloId=44448

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#USA, #California: Confirmed #H5 #Birdflu Detected in #LA County #Cats That Consumed Recalled Raw #Milk - Public Health Investigating Additional Possible Cases in Cats

 {Excerpt}

The Los Angeles County Department of Public Health has confirmed two cases of H5 bird flu in cats that consumed recalled raw milk from Raw Farm, LLC. In addition, Public Health is investigating three other possible cases of H5 bird flu in three cats from a different household.

The confirmed two infected indoor cats from one household consumed raw milk linked to a recall of raw milk and cream products prior to onset of symptoms, which included lack of appetite, fever and neurologic signs. The infected cats died after severe worsening of their illness, and subsequently tested positive for Influenza A, a rare result in cats. Public Health received the results of confirmatory testing, which confirmed the infection of H5 bird flu. Additional pets in the home are under quarantine.

Public Health is now investigating additional possible cases of H5 bird flu in three cats from a different household. One cat has tested positive for Influenza A, a rare result in cats. Two other cats, which have died after worsening respiratory illness, are presumed to have also been positive for Influenza A. Public Health is awaiting confirmatory testing. These cats were not known to be exposed to raw milk, however public health is investigating other possible sources of infection, including raw meat.

The nationwide H5 bird flu outbreak has seen other cats infected with the virus after consuming infected raw milk.

People who had direct contact with the cats are monitoring for symptoms and have been offered antiviral prophylaxis. There have been no human cases of bird flu associated with exposure to these cats yet identified. The investigation is ongoing.

Although human cases of bird flu are rare and the risk to residents remains low, this detection of H5 bird flu in cats who consumed raw milk underscores the importance of being proactive about preventing ongoing transmission of the virus.

“The risk of H5 bird flu remains low in Los Angeles County, but these confirmed cases of the virus in pet cats are a reminder that consuming raw dairy and meat products can lead to severe illness in cats," said Dr. Barbara Ferrer, Ph.D., M.P.H., M.Ed., Director of the Los Angeles County Department of Public Health. “To avoid the spread of disease, including H5 bird flu, we strongly encourage residents and their pets to avoid raw dairy and undercooked meat products, limit contact with sick or dead animals, report sick or dead birds and keep pets or poultry away from wild animals and birds.”

Cats may be exposed to H5 bird flu by consuming infected birds or other animals, being in environments contaminated with the virus, and consuming unpasteurized milk from infected cows. Cats infected with H5 bird flu may develop severe illness that can include fever and neurologic signs, and that can rapidly progress to death. Transmission of the H5 bird flu virus from mammal to mammal can occur. Cats have transmitted another influenza strain to humans, but there have been no known cases to date of H5 bird flu transmitted from cats to humans as part of this nationwide H5 bird flu outbreak.

Raw milk, which is milk that has not been pasteurized, can carry harmful germs including influenza. These germs can present serious health risks to you, your family, and your pets. Anyone can become sick from drinking raw milk or consuming raw milk products. The people at the highest risk for severe illness include people who are pregnant, adults 65 years and older, children younger than 5 years, and people with weakened immune systems.

Public Health continues to strongly encourage residents to avoid consuming raw milk and to not feed it to their pets; this includes frozen raw milk products since freezing does not eliminate harmful germs that can cause illness. Pasteurized milk remains safe to drink.

Symptoms of H5 bird flu infection in humans include eye redness or discharge, cough, sore throat, runny or stuffy nose, diarrhea, vomiting, muscle or body aches, headaches, fatigue, trouble breathing and fever.

Anyone who has consumed these specific recalled raw milk products and is experiencing symptoms should immediately contact their health care provider or local health department.

Samples from birds, cats, and wild mammals in LA County continue to be tested for H5 bird flu at our Public Health Laboratory. In addition, the Public Health Laboratory routinely tests clinical specimens from humans for H5 bird flu as part of ongoing surveillance.

(...)

Source: Los Angeles County Public Health Department, http://publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=4908

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#USA, Confirmed #H5N1 avian #flu virus #human case summary during 2024 #outbreak, by state & exposure source {as of Dec. 23: +1 case, total = 65}

{Excerpt, edited}

Exposure Source

[State - Exposure Associated with Commercial Agriculture and Related Operations: Dairy Herds (Cattle) Poultry Farms and Culling Operations - Other Animal Exposure† - Exposure Source Unknown‡ - State Total]

1) California - 35 - 0 - 0 - 1 - 36

2) Colorado - 1 - 9 - 0 - 0 - 10

3) Iowa - 0 - 1 - 0 - 0 - 1 {+1}

4) Louisiana - 0 - 0 - 1 - 0 - 1

5) Michigan - 2 - 0 - 0 - 0 - 2

6) Missouri - 0 - 0 - 0 - 1 - 1

7) Oregon - 0 - 1 - 0 - 0 - 1

8) Texas - 1 - 0 - 0 - 0 - 1

9) Washington - 0 - 11 - 0 - 0 - 11

10) Wisconsin - 0 - 1 - 0 - 0 - 1

-- Source Total - 39 - 23 - 1 - 2 - 65 {+1}

NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022.

{†} Exposure was related to other animals such as backyard flocks, wild birds, or other mammals

{‡} Exposure source was not able to be identified

Probable human case summary during the 2024 outbreak, by state and exposure source

When a case tests positive for H5 at a public health laboratory but testing at CDC is not able to confirm H5 infection, per Council of State and Territorial Epidemiologists (CSTE) guidance, a case is reported as probable.

[Probable cases with commercial poultry exposure (e.g., poultry farms or culling operations):]

-- Washington (3)

-- Arizona (2)

[Probable cases with commercial dairy (cattle) exposure:]

-- California (1)

[Probable cases with exposure source unknown:]

-- Delaware (1)

Confirmed and probable cases are typically updated by 5 PM EST on Mondays (for cases confirmed by CDC on Friday, Saturday, or Sunday), Wednesdays (for cases confirmed by CDC on Monday or Tuesday), and Fridays (for cases confirmed by CDC on Wednesday and Thursday). Affected states may report cases more frequently.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm

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#WHO #Statement on the #antigen #composition of #COVID19 #vaccines (Dec. 23 '24)

23 December 2024 - Statement 

Key points:

-- 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).

-- SARS-CoV-2 continues to circulate and evolve with important genetic and antigenic evolution of the spike protein since the beginning of the COVID-19 pandemic.

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

-- The WHO TAG-CO-VAC advises retaining the use of a monovalent JN.1 lineage variant as the antigen in future formulations of COVID-19 vaccines.

-- In accordance with WHO SAGE policy, vaccination should not be delayed in anticipation of access to vaccines with an updated composition; vaccination programmes can continue to use any available WHO emergency-use listed or prequalified COVID-19 vaccines. 

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 April 2024, the TAG-CO-VAC recommended the use of a monovalent JN.1 lineage vaccine antigen as one approach to induce enhanced neutralizing antibody responses to JN.1 and its descendent lineages.  Several manufacturers (using mRNA and recombinant protein-based vaccine platforms) have updated COVID-19 vaccine antigen composition to monovalent JN.1 lineage formulations (JN.1 or KP.2) and some of these have been approved for use by regulatory authorities. Previous statements from the TAG-CO-VAC can be found on the  WHO website.

The TAG-CO-VAC reconvened on 10-12 December 2024 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 SARS-CoV-2 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 immunogenicity data on immune responses following infection with circulating SARS-CoV-2 variants; 

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

(6) Preliminary preclinical 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 publicly available data reviewed by the TAG-CO-VAC can be found in the accompanying data annex. Unpublished and/or confidential data reviewed by the TAG-CO-VAC are not shown.

Summary of available evidence

In 2024, SARS-CoV-2 continues to circulate globally and cause severe disease, post COVID-19 condition and death. The majority of COVID-19 deaths continue to occur in individuals aged 65 years and older and those with coexisting conditions. There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, making epidemiological trends difficult to infer.

Currently circulating SARS-CoV-2 variants are all derived from JN.1. The weekly proportion of XEC sequences among all SARS-CoV-2 sequences submitted to GISAID continues to increase, while the weekly proportions of all other Variants of Interest (JN.1) or Variants Under Monitoring (KP.2, KP.3, KP.3.1.1, JN.1.18 and LB.1) are now declining. There are other JN.1-derived variants that are currently in low proportions, but which have mutations that may give them an advantage over XEC: currently LP.8.1, NP.1, LF.7.2 are variants being monitored and/or characterized.

In published and unpublished data using antisera from naïve animal models, circulating JN.1-derived variants (JN.1, JN.1.16.1, KP.2, KP.2.3, KP.3, KP.3.1.1, LB.1 and XEC) are antigenically closely related.

Analysis of naïve mice immunized with mRNA vaccine antigens (KP.3, KP.3.1.1, XEC) showed that JN.1, KP.3.1.1, XEC are antigenically closely related to each other (approximately 1 antigenic unit in cartographic analysis, which corresponds to a two-fold-reduction in neutralization). Antisera to KP.3.1.1 and XEC generate cross-reactive neutralizing antibody titers to each other and to other emerging variants.

Antisera from naïve hamsters infected with JN.1 descendent lineages showed that circulating JN.1-derived variants such as KP.3.1.1 are antigenically closely related to JN.1 and to each other (approximately 1 antigenic unit in cartographic analysis). JN.1 antisera showed greater cross-reactivity to KP.2 and KP.3.1.1, as compared to KP.2 antisera.

In published and unpublished data from humans, vaccination with monovalent JN.1 or KP.2 antigens significantly increased neutralizing antibody titers that cross-reacted with all JN.1 descendent lineages tested.

Analysis of pre- and post-vaccination sera from JN.1 or KP.2 immunized individuals demonstrated that vaccination results in strong rises in neutralizing antibody titers against JN.1 and descendent variants, including KP.2, KP.2.3, KP.3, KP.3.1.1 and XEC.

Post-monovalent JN.1 or KP.2 vaccination neutralizing antibody titers against KP.3.1.1 and XEC were modestly lower (consistent 2-fold reductions in titers) than those against the homologous JN.1 or KP.2 antigens.

There were greater reductions in cross-neutralization of emerging JN.1 lineage variants using post-monovalent XBB.1.5 vaccination sera, as compared to post-monovalent JN.1 or post-monovalent KP.2 vaccination sera.

In a context of infection- and vaccine-derived immunity in the majority of the population, contemporary vaccine effectiveness (VE) estimates are relative (rVE) rather than absolute (comparing vaccinated to unvaccinated individuals). rVE, sometimes referred to as “up-to-date VE”, demonstrates the added protection of most recent vaccination over and above pre-existing immunity derived from previous infections and/or vaccinations. There are currently studies reporting VE or rVE estimates using monovalent JN.1 lineage (JN.1 or KP.2) vaccines.  

Approved monovalent XBB.1.5 mRNA COVID-19 vaccines continued to provide additional protection against severe disease and death during periods of XBB descendent lineage circulation in the first three months after vaccination; rVE point estimates against symptomatic disease were typically lower. During periods of JN.1 descendent lineage circulation, monovalent XBB.1.5 mRNA vaccines continued to show additional protection in the first three months after vaccination, however, available evidence points towards a reduction in rVE estimates against JN.1-derived variants, as compared to XBB.1 lineage variants, for protection against death, severe disease, symptomatic disease and infection.

The VE estimates for monovalent XBB.1.5 vaccines against JN.1-derived variants are consistent with reductions in neutralizing antibody titers observed in preclinical and clinical immunogenicity studies of post-monovalent XBB.1.5 vaccination sera against JN.1 descendent variants, as compared to XBB.1 lineage variants.

Preclinical data shared confidentially with the TAG-CO-VAC by vaccine manufacturers show that immunization of naïve mice, as well as of mice previously immunized with SARS-CoV-2 variants with monovalent JN.1-containing or monovalent KP.2-containing vaccine candidates resulted in good neutralization of JN.1 and descendent variants, including KP.3.1.1, XEC and MC.1. However, neutralizing antibody titers against KP.3.1.1, XEC and MC.1 were approximately 2-fold lower than those against the homologous immunizing antigen. A single preclinical immunogenicity study in mice using an XEC vaccine candidate showed comparable neutralizing antibody titers against JN.1, KP.3.1.1 and XEC as compared to a JN.1 vaccine candidate.

Clinical data shared confidentially with the TAG-CO-VAC by vaccine manufacturers show that post-monovalent JN.1 sera neutralized JN.1 and its derivatives including KP.3.1.1 and XEC well.

The TAG-CO-VAC acknowledges several limitations of the 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) 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. There are JN.1-derived variants such as LP.8.1, NP.1 and LF.7.2 that are currently in low proportions, but which have mutations that may give them more immune escape than XEC. These will continue to be monitored and/or characterized. 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 XBB.1.5 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. Further, there are very limited data on immune responses following infection in humans with recent SARS-CoV-2 variants (e.g., KP.3.1.1, XEC).

-- Estimates of VE against recently circulating SARS-CoV-2 variants, including XBB or JN.1 descendent lineages, are limited in terms of the number and geographic diversity of studies, vaccine platforms evaluated, populations assessed, and duration of follow-up. Furthermore, the referent population for VE estimates varies substantially with respect to prior history of vaccination. There are currently no direct comparative estimates for monovalent JN.1, KP.2 or XBB.1.5 vaccines versus other antigen composition(s) delivered during the same time period. Finally, VE estimates may be confounded by differences in undocumented infection-derived immunity between groups, leading to potential underestimation of VE.

Recommendations for COVID-19 vaccine antigen composition

Given the breadth in immune responses demonstrated by monovalent JN.1 lineage vaccines against circulating variants, the TAG-CO-VAC advises retaining the current COVID-19 vaccine antigen composition, i.e. a monovalent JN.1 lineage variant (NextStrain: 24A, GenBank: PP298019, GISAID: EPI_ISL_18872762) as one approach to induce enhanced neutralizing antibody responses to JN.1 and its descendent variants (e.g., KP.3.1.1 and XEC).

Other approaches that demonstrate broad and robust neutralizing antibody responses against currently circulating JN.1 descendent lineage variants, such as vaccine antigens derived from more recent variants or alternative formulations, 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. Vaccination should not be delayed in anticipation of access to vaccines with an updated composition; vaccination programmes can continue to use any available WHO emergency-use listed or prequalified COVID-19 vaccines.

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 October 2024): 

-- Immune responses and clinical endpoints (i.e. VE and/or comparator rates of infection and severe disease) in varied human populations who receive COVID-19 vaccines with a monovalent JN.1 or KP.2 vaccine antigen composition, across different vaccine platforms, as well as further clinical and laboratory data on the performance of all currently approved COVID-19 vaccines against emerging SARS-CoV-2 variants.

-- 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.

-- Clinical evaluation of relevant new vaccine antigens derived from more recent variants.

-- 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 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.

Source: World Health Organization, https://www.who.int/news/item/23-12-2024-statement-on-the-antigen-composition-of-covid-19-vaccines

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