CDC Statement On Spring COVID Vaccine For Seniors

#17,931

Yesterday the CDC's ACIP (Advisory Committee on Immunization Practices) - after reviewing the evidence - recommended people 65 and older receive an additional dose of the current monovalent  COVID-19 vaccine this spring.

Late yesterday the CDC published the following statement in support of that recommendation. 

Older Adults Now Able to Receive Additional Dose of Updated COVID-19 Vaccine

Media Statement

For Immediate Release: Wednesday, February 28, 2024
Contact: Media Relations
(404) 639-3286


Today, CDC Director Mandy Cohen endorsed the CDC Advisory Committee on Immunization Practices’ (ACIP) recommendation for adults ages 65 years and older to receive an additional updated 2023-2024 COVID-19 vaccine dose. The recommendation acknowledges the increased risk of severe disease from COVID-19 in older adults, along with the currently available data on vaccine effectiveness.

Previous CDC recommendations ensured that people who are immunocompromised are already eligible for additional doses of the COVID-19 vaccine.

Data continues to show the importance of vaccination to protect those most at risk for severe outcomes of COVID-19. An additional dose of the updated COVID-19 vaccine may restore protection that has waned since a fall vaccine dose, providing increased protection to adults ages 65 years and older.

Adults 65 years and older are disproportionately impacted by COVID-19, with more than half of COVID-19 hospitalizations during October 2023 to December 2023 occurring in this age group.

CDC and ACIP will continue to monitor COVID-19 vaccine safety and effectiveness. CDC continues to recommend that everyone stay up to date on their COVID-19 vaccines, especially people with weakened immune systems.

The following is attributable to Dr. Mandy Cohen:

“Today’s recommendation allows older adults to receive an additional dose of this season’s COVID-19 vaccine to provide added protection,” said Mandy Cohen, M.D., M.P.H. “Most COVID-19 deaths and hospitalizations last year were among people 65 years and older. An additional vaccine dose can provide added protection that may have decreased over time for those at highest risk.”

ACIP will meet in June to review the evidence for next fall's vaccine as illustrated by the following two slides from yesterday's Next Steps for the COVID-19 Vaccine Program presentation. 

 

EID Journal: HPAI A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023

#17,930

The rapid spread of HPAI H5N1 down the length of South America - which began in the fall of 2022 - brought with it numerous reports of marine mammal die offs (see EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)), along with the loss of hundreds of thousands of wild birds.

Although we've long known that marine mammals (seals, whales, sea lions, otters, etc.) are susceptible to influenza viruses (see UK: HAIRS Risk Assessment On Avian Flu In Seals) - we've never seen anything quite like the losses due to HPAI H5 over the past 16 months in South America.

Along the way we've seen indications that as HPAI H5 has spilled over into marine mammals, it has acquired a number mammalian host adaptations.  Small amino acid changes that make it more suitable for carriage in non-avian species. 

In last November's EID Journal: Highly Pathogenic Avian Influenza A(H5N1) from Wild Birds, Poultry, and Mammals, Peru, the authors cited:

2 mutations in the polymerase basic 2 protein (Q591K and D701N) associated with mammal adaptation were identified only in sequences from sea lions in Peru and from 1 human case in Chile.

Today we've a research letter, published in the EID Journal, from University of California, Davis, and the National Institute of Agricultural Technology (INTA) in Argentina, that characterizes the full genome of the HPAI H5N1 virus collected from samples taken from four sea lions, one fur seal and a tern last August.

They found the same two mutations (Q591K and D701N) described above in the Peruvian study, along with others, which suggest that the virus has adapted to mammalian hosts, while still retaining the ability to infect birds. 

They authors also state that, based on the available evidence, `. . . it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region.'

You'll find a less technical summary in the following press release from the UNIVERSITY OF CALIFORNIA - DAVIS, followed by a link to, and some excerpts from the full EID article. 

Avian influenza virus is adapting to spread to marine mammals

Findings raise concerns about wildlife conservation and ecosystem health

The highly pathogenic avian influenza virus H5N1 has adapted to spread between birds and marine mammals, posing an immediate threat to wildlife conservation, according to a study from the University of California, Davis, and the National Institute of Agricultural Technology (INTA) in Argentina.

The study, published in the journal Emerging Infectious Diseases, is the first genomic characterization of H5N1 in marine wildlife on the Atlantic shore of South America.

          (SNIP)

Genome sequencing revealed that the virus was nearly identical in each of the samples. The samples shared the same mammal adaptation mutations that were previously detected in a few sea lions in Peru and Chile, and in a human case in Chile. Of note, the scientists found all these mutations also in the tern, the first such finding.

“This confirms that while the virus may have adapted to marine mammals, it still has the ability to infect birds,” said first author Agustina Rimondi, a virologist from INTA. “It is a multi-species outbreak.”

We know this because the virus sequence in the tern retained all mammal-adaptation mutations. Such mutations suggest a potential for transmission between marine mammals.

          (Continue . . . )

Research Letter
Highly Pathogenic Avian Influenza A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023

Agustina Rimondi , Ralph E.T. Vanstreels, Valeria Olivera, Agustina Donini, Martina Miqueo Lauriente, and Marcela M. Uhart

Abstract

We report full-genome characterization of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus from an outbreak among sea lions (August 2023) in Argentina and possible spillover to fur seals and terns. Mammalian adaptation mutations in virus isolated from marine mammals and a human in Chile were detected in mammalian and avian hosts.


In February 2023, the first case of highly pathogenic avian influenza (HPAI) A(H5N1) in Argentina was detected in a wild goose near the border with Bolivia and Chile (Appendix Figure 1) (1). In contrast with Peru and Chile, where extensive mortality of seabirds and marine mammals had been attributed to the virus in the preceding months (2,3), the initial spread of HPAI H5N1 in Argentina was largely limited to backyard and industrial poultry (94 outbreaks), causing the death or disposal of 2.2 million birds. Argentina declared itself free from the disease in poultry on August 8, 2023; before then, HPAI H5N1 detections in wildlife in Argentina had been scarce (7 events during February–April) and limited to aquatic birds (Anatidae, Laridae, and Rallidae) (1,4).

However, soon thereafter, the national animal health services confirmed HPAI H5N1 in South American sea lions (Otaria byronia) from Río Grande, southernmost Argentina. Over subsequent weeks, the virus was detected in sea lions northward along the Argentina coast, and sporadic cases also occurred in South American fur seals (Arctocephalus australis). The most affected site was Punta Bermeja (Appendix Figure 1), the largest sea lion colony in Argentina, where an estimated 811 sea lions died over 2 months; minimal numbers (<5) of fur seals and terns were also affected (1,4).

In collaboration with provincial authorities and park rangers, we collected swab samples (oronasal, rectal, tracheal, lung, and brain) from 16 deceased sea lions, 1 fur seal, 1 great grebe (Podiceps major), and 1 South American tern (Sterna hirundinacea) discovered at Punta Bermeja on August 26, 2023. A sampled adult male sea lion was seen alive showing clinical signs consistent with HPAI infection (inability to stand or walk, muscular tremors and spasms, difficulty breathing, and abundant oral mucus). We tested the samples by real-time reverse transcription PCR targeting influenza A virus (5) and confirmed that all were positive. On the basis of viral RNA yields, we selected brain samples from 4 sea lions, 1 fur seal, and 1 tern for full-genome sequencing (Appendix Figure 2). We used maximum-likelihood tree phylogenetic analysis (6) and mutational analysis to compare the sequences (GenBank accession nos. OR987081–128) with representative HPAI H5N1 strains from South America.

Phylogenetic trees (Figure; Appendix Figure 2) showed that the viruses we identified belong to HPAI H5N1 clade 2.3.4.4b and are closely related to H5N1 viruses that circulated in South America during 2022–2023. Our finding supports the hypothesis that, after introduction from North America into Peru in November 2022, HPAI H5N1 viruses continued spreading across the continent and into Argentina. Of note, the viruses from Punta Bermeja did not cluster with the hemagglutinin and neuraminidase sequences available from HPAI H5N1 first detected in a wild goose in Argentina. Instead, all gene segments from the viruses were closely related to virus sequences from sea lions in Chile and Peru (2; C. Pardo Roa, unpub. data, https://www.biorxiv.org/content/10.1101/2023.06.30.547205vExternal Link); 6 gene segments (all except polymerase basic protein 1 and nucleocapsid protein) also clustered with the virus isolated from a human in Chile (7). T

hat finding suggests that viruses from Punta Bermeja may have been derived from a separate HPAI H5N1 introduction into Argentina. Because of the lack of genomic data for HPAI H5N1 viruses circulating in Argentina during February–July 2023, the finer scale pathways (local geographic routes and host species involved) of how these viruses arrived at Punta Bermeja remain unclear. Even so, the viruses that we report did not cluster with those from birds in Uruguay, Brazil, or Bird Island (Antarctica), possibly suggesting separate pathways of virus spread.

On the basis of previous comparisons with HPAI H5N1 isolates from other countries in South America, we identified 9 mutations already present in viruses infecting sea lions in Peru and Chile but not in the goose/Guangdong reference strain or in viruses from birds and mammals from North America in 2022 (Table). Specifically, we found Q591K and D701N mutations in polymerase basic 2 associated with increased pathogenicity to mammals (8). The virus we detected in the tern from South America also has those mutations, but they were absent from previously reported HPAI H5N1 viruses from avian hosts in South America (except for A/sanderling/Arica y Parinacota/240265/2023, which has the D701N mutation).

That finding further supports the hypothesis that HPAI H5N1 viruses from sea lions from Peru and Chile acquired mammalian adaptation mutations that improved their ability to infect pinnipeds while possibly retaining the ability to infect avian hosts.

Given the rapid and widespread dissemination of the viruses among pinnipeds in South America and the substantial associated mortalities (3,9), it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region. It is alarming that the HPAI H5N1 viruses infecting pinnipeds and seabirds in Argentina share the same mammalian adaptation mutations as the virus from the affected human in Chile, which highlights the potential threat posed by these viruses to public health.

Dr. Rimondi is a scientist at the National Institute of Agricultural Technology in Argentina and a postdoctoral fellow from Alexander von Humboldt Foundation from Germany working on HPAI H5N1 at the Robert Koch Institute. Her primary research interests focus on molecular epidemiology and host–pathogen interactions of avian influenza viruses.

This isn't the first time that we've seen the possibility of seal-to-seal transmission discussed, but proving it has been difficult.  While not definitive proof, this latest study certainly adds scientific credence to the idea, and reminds us that HPAI H5Nx continues to evolve in the wild. 

While it is still possible there is some species barrier that prevents HPAI H5 from posing a pandemic threat - it continues to expand both its geographic and host range - making it too unpredictable to ignore. 

Another Brief Hiatus

 

Since the first surgery went so well, I'll be leaving in a couple of hours to have my second cataract operation, which means I probably won't be blogging again until tomorrow afternoon (or possibly) Thursday morning. 

In the meantime, you can check in with FluTrackers and with CIDRAP or Crof for the latest infectious disease news.

Cheers, and thanks for all the visits to this humble blog over the years.

PLoS Pathogens: Species-specific Emergence of H7 HPAI Virus is Driven by Intrahost Selection Differences Between Chickens and Ducks

 

#17,929

The avian flu threat we were facing a decade ago (Feb 2014) was far different from what we see today. The HPAI H5 threat was still concentrated in Asia, the Middle East, and Western Africa - with the virus making only occasional, short-lived, forays into Europe. 

Although we'd seen some evidence of long-distance carriage of HPAI viruses by migratory birds, their role in spreading the virus was still very much a matter of bitter debate (see Bird Flu Spread: The Flyway Or The Highway?). 

While a newly emerging HPAI H5N8 would appear in South Korean poultry in early 2014 with an improved ability to be carried by migratory birds (see J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade 2.3.4.4), LPAI H5 and H7 viruses have another parlor trick; the ability to spontaneous mutate into an HPAI strain. 

Now that HPAI viruses like H5N1 are more easily winging their way around the globe in migratory birds, that may seem less important, but this remains a credible route for seeing new HPAI H5 and H7 viruses emerge. 

Our understanding of how this happens is limited, and is based primarily on observations from a few dozen documented incidents in poultry, but it prompted the OIE (now WOAH) to make LPAI H5 and H7 viruses reportable in 2006, and infected captive birds subject to immediate eradication (see Terrestrial Animal Code Article 10.4.1.).

HPAI viruses have been generated in the lab by repeated passage of LPAI viruses through chickens (cite FAO) but exactly how and why this occurs naturally is poorly understood (see JVI Emergence of a Highly Pathogenic Avian Influenza Virus from a Low Pathogenic Progenitor).

All of which brings us to a new research article in PLoS Pathogens which describes experiments where both poultry and wild ducks were inoculated with LPAI and HPAI H7N7 viruses, and the resultant spread and/or mutation of these viruses. 

This is a lengthy, and at times highly technical report, that seems to bear out the theory that spontaneous LPAI-to-HPAI mutations are far more likely to occur in poultry than in wild ducks. Furthermore, HPAI H7N7 viruses had difficulty competing with LPAI strains in wild ducks. 

Due to its length, I've only posted the link, Abstract, and Author's summary. I'll have a bit more after the break.  

Species-specific emergence of H7 highly pathogenic avian influenza virus is driven by intrahost selection differences between chickens and ducks

Anja C. M. de Bruin, Monique I. Spronken, Adinda Kok, Miruna E. Rosu, Dennis de Meulder,Stefan van Nieuwkoop, Pascal Lexmond, Mathis Funk, Lonneke M. Leijten, Theo M. Bestebroer, Sander Herfst, Debby van Riel,Ron A. M. Fouchier,Mathilde Richard 

Published: February 26, 2024

https://doi.org/10.1371/journal.ppat.1011942

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) cause severe hemorrhagic disease in terrestrial poultry and are a threat to the poultry industry, wild life, and human health. HPAIVs arise from low pathogenic avian influenza viruses (LPAIVs), which circulate in wild aquatic birds. HPAIV emergence is thought to occur in poultry and not wild aquatic birds, but the reason for this species-restriction is not known. 

We hypothesized that, due to species-specific tropism and replication, intrahost HPAIV selection is favored in poultry and disfavored in wild aquatic birds. We tested this hypothesis by co-inoculating chickens, representative of poultry, and ducks, representative of wild aquatic birds, with a mixture of H7N7 HPAIV and LPAIV, mimicking HPAIV emergence in an experimental setting. Virus selection was monitored in swabs and tissues by RT-qPCR and immunostaining of differential N-terminal epitope tags that were added to the hemagglutinin protein. 

HPAIV was selected in four of six co-inoculated chickens, whereas LPAIV remained the major population in co-inoculated ducks on the long-term, despite detection of infectious HPAIV in tissues at early time points. Collectively, our data support the hypothesis that HPAIVs are more likely to be selected at the intrahost level in poultry than in wild aquatic birds and point towards species-specific differences in HPAIV and LPAIV tropism and replication levels as possible explanations.

Author summary

Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in poultry with mortality rates reaching 100% and, therefore, pose a large burden on the poultry industry. Additionally, some HPAIVs have spilled back from poultry into wild bird populations, increasing their geographic spread. HPAIVs arise from low pathogenic avian influenza viruses (LPAIVs), which circulate in wild aquatic birds and occasionally spillover into poultry. 

LPAIV to HPAIV conversion is associated with terrestrial poultry species, but the reasons underlying this species-restriction are unknown. The second step of HPAIV emergence, following HPAIV genesis, constitutes of the intrahost selection of the HPAIV from the large pool of replicating LPAIVs. Here, we investigated whether the intrahost selection efficiency differs between chickens and ducks, models for poultry and wild aquatic birds respectively, by co-inoculating them with HPAIV and LPAIV. Tagged viruses were utilized to monitor LPAIV and HPAIV frequencies at both the RNA and protein level. The HPAIV was selected in a majority of the chickens, demonstrated by the development of canonical HPAI disease and infectious HPAIV shedding, whereas all ducks solely shed infectious LPAIV. These results confirm that intrahost selection of HPAIVs is species-specific, which likely contributes to the restriction of HPAIV-emergence to poultry populations.

          (Continue . . . )

This study is subject to a number of limitations, including the use of a single subtype (H7N7) of avian influenza, and the use of ducks as a proxy for all aquatic bird species. 

It is possible that the use of a different subtype (i.e. newer HPAI H5 viruses), or a broader range of avian hosts, might return somewhat different results. 

That said, these findings are consistent with earlier studies showing that spread in poultry is far more likely to convert an LPAI H5 or H7 virus into an HPAI virus, than in wild or aquatic birds. 

The demonstrated inability of HPAI H7N7 to compete with LPAI viruses in infected ducks is reminiscent of what we were seeing with HPAI H5 prior to 2016 (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl).

Carriage of HPAI H5 viruses by aquatic birds was generally short-lived, restricting its spread. 

 

But a series of evolutionary changes to HPAI H5Nx clade 2.3.4.4b in recent years has made it possible for HPAI H5 to be carried, sometimes asymptomatically, by a wide variety of avian hosts.  Over the past 3 years we've seen this new-and-improved HPAI H5 virus spread to nearly every corner of the globe. 

While today we are focused primarily on HPAI H5, this ability for LPAI H5 and H7 viruses to mutate into HPAI variants means that if we fail to control LPAI viruses in poultry, we could see another contender emerge from almost anywhere, and at anytime, with little or no notice. 

Viruses: Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice

 

A classic serial passage experiment showing Host adaptation 

#17,928

In the summer of 2013 Taiwan's CDC Reported the 1st Human Infection With Avian H6N1, detected in a 20 year-old female who was hospitalized for pneumonia. The case might have gone undiagnosed were it not for the enhanced surveillance for H7N9, which had broken out in Mainland China a few months earlier.

Three years earlier, researchers had reported the Identification of an H6N6 swine influenza virus in southern China.

Over the next few years we'd see additional evidence suggesting that avian H6 viruses - which are ubiquitous in wild birds and poultry - could someday pose a potential threat to human health. 

• In 2014 we learned that H6N1 had jumped to Taiwanese dogs (see Taiwan: Debating The Importance Of H6N1 In Dogs)
• In 2015, in  EID Journal: Seropositivity For H6 Influenza Viruses In China - researchers reported on a small, but significant number of people in their survey who tested positive for H6 influenza antibodies (indicating previous exposure).
• Also in 2015, in Study: Adaptation Of H6N1 From Avian To Human Receptor-Binding, we saw a report citing changes the authors suggest are slowly moving the H6N1 virus towards preferential binding to human receptor cells instead of avian receptor cells
• In 2020's Nature: Evolution & Pathogenicity of H6 Avian Influenza Viruses, Southern China 2011-2017, we looked at H6's increasing adaptation to mammalian physiology,
• And in 2022 we saw  Study: Influenza A (H6N6) Viruses Isolated from Chickens Replicate in Mice and Human lungs Without Prior Adaptation which found binding to both avian-like and human-like receptors.

More recently, in November of 2023 in Emerg. Microbes & Inf.: Epidemiology, Evolution, and Biological Characteristics of H6 Avian Influenza Viruses in China, we looked at a study by Chinese researchers which characterized the evolution and biological characteristics of H6 viruses, and produced  additional evidence of increased adaptation to mammalian hosts.

While avian H6 viruses don't get a lot of press, they continue to reassort, evolve, and spillover into non-avian species. With each spillover comes an opportunity to better adapt to mammalian hosts, a process which is demonstrated by the serial passage graphic at the top of this blog.

Essentially, you inoculate a host (mouse, ferret, guinea pig, etc.) with a `wild type’ strain of a virus - let it replicate for awhile - then take the virus from the first host and inoculate a second, and then repeat the process five, ten, fifteen times or more.

Over time, the virus tends to adapt to the new host (assuming there are no species barriers to prevent it), often increasing replication, virulence, and/or transmissibility.

Which is precisely what the following study demonstrates; that after only a single passage through BALB/c mice, a wild bird-origin H6N2 virus picked up two significant mutations (PB2 E627K and HA A110V) increasing both its replication and lethality in mice.

While in this case the passage-generated mutant retained its avian α-2, 3-linked sialic acid binding property, we've seen other studies showing avian H6 viruses with an affinity for both avian and human (α-2, 6-linked sialic acid) receptor cells.

This is a lengthy and detailed report, and I've only posted the Abstract and some excerpts. Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice
by Siqi Tang, Bing Han, Chaofan Su, Hailing Li, Shiyuchen Zhao, Haoyu Leng, Yali Feng and Ying Zhang 

Viruses 2024, 16(3), 357; https://doi.org/10.3390/v16030357 (registering DOI)

Published: 25 February 2024

The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. 

In this study, a wild bird-origin H6N2 AIV was isolated from the East Asian–Australasian migratory flyway region located in Liaoning Province. This H6N2 virus initially expressed limited replication in mice. However, after one passage in mice, the virus acquired two mutations, PB2 E627K and HA A110V. 

The mutant displayed enhanced replication both in vitro and in vivo, proving lethal to mice. But the mutant retained the α-2, 3-linked sialic acid binding property and failed to transmit in guinea pigs. 

We explored the molecular mechanisms underlying the pathogenicity difference between the wild type and the mutant. Our findings revealed that PB2 E627K dramatically enhanced the polymerase activity of the H6N2 virus, while the HA A110V mutation decreased the pH of HA activation. This study demonstrated that the H6N2 subtype wild bird-origin AIV easily acquired the mammalian adaptation. The monitoring and evaluation of H6 wild bird-origin AIV should be strengthened.

(SNIP)

4. Discussion

Wild birds are generally considered to be the natural hosts of AIVs. Liaoning is located on the East Asian–Australasian flyway route and possesses several migrating stopovers and wintering areas for wild birds. In this study, we isolated and purified an H6N2 subtype wild bird-origin AIV, A/wild bird/Liaoning/DD535/2021 (DD535), in April 2021 from a wetland in Liaoning. Although DD535 exhibited limited replication ability in mice, it acquired two mutations, PB2 E627K and HA A110V, during the first round of infection. These mutations endowed this H6N2 virus with enhanced polymerase activity and decreased the pH of HA activation, ultimately enhancing lethality to mice.

H6 subtype AIVs belong to the low pathogenic AIV and have become one of the most prevalent subtypes worldwide. Previous studies have demonstrated that some of the H6 AIVs isolated from poultry were able to bind α-2,6 SA receptors and transmit among mammalian hosts [7]. The H6 subtype AIVs have already shown the potential to threaten public health.

Genetic recombination and mutations are considered to be the two major mechanisms of AIVs adapting to new hosts. Three of the four human influenza pandemics of the last century were caused by genetic reassortment of influenza viruses. Recent genetic reassortment events were observed in emerging H5N1 [34], H7N9 [35], H10N8 [36], and H5N6 [37]. Most of these reassortants acquired human infectivity. Genetic mutation could occur rapidly once AIV is introduced into other species. Numerous adaptive mutations were detected during avian-origin viruses spilling into mammalian hosts. For example, the H7N9 AIVs in 2013 in China were nonpathogenic for poultry and mice but obtained the PB2 627K or PB2 701N mutation during replication in ferrets, leading to high lethality in mice and ferrets [38]. Our results indicated that the H6N2 subtype wild bird-origin AIV could acquire two adaptive mutations, PB2 E627K and HA A110V, after only one passage in mice. The mutant strain had increased tissue tropism and pathogenicity in mice. Additionally, it exhibited increased replication ability in mammalian cells and enhanced replication efficiency in guinea pigs.

As early as 1993, PB2 E627K was recognized as a determinant of virulence and host range [39]. Subsequent studies revealed multiple functions of PB2 E627K, such as enhancing AIV polymerase activity, replication, and transmissibility in mammals [40,41,42]. In our study, PB2 E627K increased the H6N2 virus polymerase activity in HEK293T cells. HA affects multiple biological characteristics of AIVs, including receptor binding property and membrane fusion, which have been proved critical in determining the host range and pathogenicity of AIVs. Amino acid positions 226 and 228 in the HA protein are associated with receptor binding properties. Both DD535 and Mut-DD535 contained 226Q/228G, suggesting a preference for binding to the avian receptor. The receptor binding assay in our study also confirmed that HA A110V did not affect the receptor binding property of the H6N2 virus. However, our findings indicated that the HA A110V mutation was responsible for the decreased pH required for membrane fusion, which might contribute to the higher replication and pathogenicity of H6N2 viruses in mice. Whether the HA A110V and PB2 E627K mutations acted synergistically or whether host factors were involved during the mutation acquisition still deserve further investigation.

5. Conclusions

In summary, we found that the wild bird-origin H6N2 subtype AIV can infect mice without prior adaptation and can rapidly acquire adaptive mutations, HA A110V and PB2 E627K, in mice. A mutant H6N2 virus with these adaptations after a single passage in mice not only exhibited higher replication ability in vitro and in vivo but also enhanced pathogenicity in mice. We further investigated the effects of HA A110V and PB2 E627K and found that HA A110V decreased the pH of the viral membrane fusion, and PB2 E627K increased the viral polymerase activity. Our research indicated that wild bird-origin H6 viruses have zoonotic potential. Continued surveillance and investigation of the H6 influenza viruses circulating in wild birds are needed.

          (Continue . . . )

Since LPAI H6 viruses only rarely produce clinical illness in poultry, and are not legally reportable to the OIE (now WOAH), we are only rarely aware of their presence, or of the potential threat they may pose.   

While the conventional wisdom is that H6 viruses are unlikely to pose a serious zoonotic threat, a dozen years ago LPAI H7 viruses were thought to be a weak cousin of HPAI H5N1, and incapable of producing the same level of virulence or spread in humans.

The emergence of LPAI H7N9 in China in 2013 - with a mortality rate (among those hospitalized) of 30% - has since dispelled that notion. A severe human infection with LPAI H7N4 in China in 2018 showed this was not a fluke.

While our attentions remain firmly fixed on HPAI H5Nx, there are a lot of `lesser' novel flu threats in the wild, quietly mutating and evolving, which could - through a lucky mutation or reassortment event -  go to the top of our pandemic worry list overnight. 

With influenza viruses, the only constant is change.  Which is why we need to be prepared to pivot the next time the unexpected happens. 

European Medicines Agency CHMP Approves 2 H5N1 Vaccines For Human Use

 

BSL-3 – Credit CDC PHIL

#17,927

Despite its recent high-profile gains in both its geographic and host range, including occasional spillovers into humans, avian H5N1 has yet to acquire the ability to spread from human-to-human in a sustained or efficient manner.  

A limitation that, hopefully, will continue to prevent it from sparking a human pandemic.  

But for the better part of two decades H5Nx has been at or near the top of our pandemic worry list, and as a result a number of H5N1 pandemic vaccines have been created, tested, and sometimes stockpiled  along the way. 

The path hasn't always been easy.

Early experimental H5 (and H7) avian flu vaccines proved poorly immunogenic – requiring unusually large amounts of antigen (up to 12x normal). Adding an adjuvant - spread across two shots several weeks apart - produced a much better immune response (see 2015's JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant).

Vaccine skepticism being what it is, how willing Americans will be to accept an adjuvanted vaccine (which have been used successfully in Europe for years), remains to be seen.  This from the CDC:

What is an adjuvant and why is it added to a vaccine?

An adjuvant is an ingredient used in some vaccines that helps create a stronger immune response in people receiving the vaccine. In other words, adjuvants help vaccines work better. Some vaccines that are made from weakened or killed germs contain naturally occurring adjuvants and help the body produce a strong protective immune response. However, most vaccines developed today include just small components of germs, such as their proteins, rather than the entire virus or bacteria. Adjuvants help the body to produce an immune response strong enough to protect the person from the disease he or she is being vaccinated against. Adjuvanted vaccines can cause more local reactions (such as redness, swelling, and pain at the injection site) and more systemic reactions (such as fever, chills and body aches) than non-adjuvanted vaccines.

Adjuvants have been used safely in vaccines for decades.

Aluminum salts, such as aluminum hydroxide, aluminum phosphate, and aluminum potassium sulfate have been used safely in vaccines for more than 70 years. Aluminum salts were initially used in the 1930s, 1940s, and 1950s with diphtheria and tetanus vaccines after it was found they strengthened the body’s immune response to these vaccines.

Newer adjuvants have been developed to target specific components of the body’s immune response, so that protection against disease is stronger and lasts longer.

In all cases, vaccines containing adjuvants are tested for safety and effectiveness in clinical trials before they are licensed for use in the United States, and these vaccines are continuously monitored by CDC and FDA once they are approved.

Additionally, we've seen problems manufacturing H5N1 vaccine in bulk (see 2019's Manufacturing Pandemic Flu Vaccines: Easier Said Than Done), particularly in egg-based production facilities.

On Friday the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for two H5N1 vaccine formulations (Celldemic & Incellipan), both manufactured by Seqirus in the Netherlands.

Celldemic - based on an inactivated A/turkey/Turkey/1/2005 (H5N1)-like strain with the M59C.1 adjuvant - is envisioned to be an interim early-use vaccine during the opening months of an H5N1 pandemic, until a more strain specific vaccine (Icellipan) can be produced. 

The EMA announcement on Celldemic follows, after which I'll have a bit more on H5N1 vaccine development in the United States. 

Celldemic

Opinion

EMA has issued an opinion on this medicine
influenza vaccine (surface antigen, inactivated, prepared in cell cultures)

Overview

On 22 February 2024, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Celldemic, intended for active immunisation against the H5N1 subtype of Influenza A virus in adults and infants from 6 months of age and above.

The applicant for this medicinal product is Seqirus Netherlands B.V..

Celldemic will be available as a 7.5 micrograms per 0.5 ml dose suspension for injection. Celldemic is an influenza vaccine (ATC code J07BB02). It contains haemagglutinin and neuraminidase surface antigens purified from inactivated A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG 23) viruses produced in MDCK cell cultures and the adjuvant M59C.1. The Celldemic vaccine triggers an immune response against the H5N1 subtype of the influenza A virus.

The benefit of Celldemic is a robust immune response in adults and children three weeks after two doses of the vaccine given three weeks appart, as measured by haemagglutination inhibition titres against H5N1. The most common side effects in adults are pain at the injection site, fatigue, headache, malaise, myalgia and arthralgia. In children aged between 6 and 18 years, the most common side effects are injection site pain, myalgia, fatigue, malaise, headache, loss of appetite, nausea, and arthralgia. In children 6 months to less than 6 years of age, the most common side effects are tenderness at the injection site, irritability, sleepiness, change in eating habits and fever.

The full indication is:

Celldemic is indicated for active immunisation against H5N1 subtype of Influenza A virus in adults and infants from 6 months of age and above.

Celldemic should be used in accordance with official recommendations.

Detailed recommendations for the use of this product will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

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The United States approved an adjuvanted monovalent H5Nx vaccine from Seqirus back in early 2020 (see FDA approval letters), and there are likely reserves of older H5Nx vaccines still in the strategic stockpile (see Vaccine: Safety & Immunogenicity Of H5N1 Vaccine Stored Up To 12 Years).

The United States government has recently entered into contracts with Seqirus to provide bulk antigen and 150 million doses (enough for 75 million people) of the vaccine within 6 months of an influenza pandemic declaration in the United States. 

Excerpts from an August 2023 Seqirus press release follow:

Under the terms of the agreement, CSL Seqirus will deliver one bulk lot of H5N8 A/Astrakhan antigen to support the U.S. government's pandemic response readiness. This is the third award CSL Seqirus has received from BARDA related to the ongoing outbreak of HPAI, following the February 2022 award to produce an H5N8 A/Astrakhan virus vaccine seed and subsequent October 2022 announcement of the selection of CSL Seqirus to deliver an H5N8 A/Astrakhan virus vaccine candidate for assessment in a Phase 2 clinical study. CSL Seqirus has been working together with BARDA in a longstanding partnership for more than a decade, which has included numerous R&D and manufacturing activities and awards in support of BARDA's pandemic preparedness objectives.

CSL Seqirus used its cell-based influenza vaccine technology, as utilized for FDA-approved AUDENZ™ (Influenza A(H5N1) Monovalent Vaccine, Adjuvanted), to manufacture the H5N8 A/Astrakhan bulk vaccine at the company's Holly Springs, North Carolina, facility, which was built in partnership with BARDA. In 2022, the Holly Springs facility successfully achieved all of BARDA's criteria required to establish domestic manufacturing capability for innovative cell-based seasonal and pandemic influenza vaccines. CSL Seqirus established and will maintain the required pandemic readiness to deliver 150 million doses of cell-based pandemic influenza vaccine within six months of an influenza pandemic declaration in the U.S.

This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50122D00004.

Until a pandemic strain of H5Nx emerges, we won't know how effective any of these preexisting vaccines will be. But even if they prove highly effective, they are likely to be in fairly short supply during the first year of a pandemic.  

Fortunately, we have several influenza antivirals (oseltamivir, oral baloxavir, inhaled zanamivir, or intravenous peramivir) that are expected to significantly reduce morbidity and mortality from H5N1.

Whether we will have enough, and are able to get them to the people who will need it within 48 hours of falling ill (see CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir), are unknowns.

H5Nx is obviously not guaranteed to spark the next influenza pandemic, as there are plenty of other influenza A subtypes on our radar (including H1, H2, H3, H6, H7, H9 & H10 viruses).  The next pandemic may not even be an influenza virus. 

There are plenty of other candidates, including MERS-CoV, Nipah, Langya, Lassa Fever, and even Virus X - the one we don't know about yet.

For more on what the CDC and the rest of the world are doing to prepare for an H5 influenza pandemic, you may wish to visit 2023's.

How The WHO & CDC Are Developing Candidate H5N1 Vaccines

Frontiers Pub. Health: The Effect of Nonpharmaceutical Interventions (NPIs) on Influenza Virus Transmission

Photo Credit PHIL (Public Health Image Library)

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Although their use was rare in western cultures, long before COVID burst onto the scene in late 2019 protective face masks were a common fashion accessory in Asia during flu season.  

So much so, that nearly a month before the first reports emerged out of Wuhan China, I wrote a `routine' blog about their use during Hong Kong's upcoming flu season (see HK CDW: Surgical Masks For Respiratory Protection).

Figure 2 - How to wear a surgical mask. (Source: The Centre for Health Protection of the Department of Health.

In that blog I wrote about the history of using face masks in Asia, one which goes back at least 100 years to the 1918 pandemic. Masks were used again after the great Tokyo earthquake and firestorm of 1923 to filter out the smoke and ash the lingered for months following the disaster.

Reinforced over the years by SARS, bird flu, three influenza pandemics, air pollution, and life in densely populated cities, the wearing of surgical masks in Asia has become commonplace.  

The use of NPIs (nonpharmaceutical interventions) like protective face masks, hand washing, and social distancing have long been a mainstay of pandemic planning (see 2017's Community Pandemic Mitigation's Primary Goal : Flattening The Curve), particularly during the opening months when no vaccine can be reasonably expected. 

While many people (understandably) don't like wearing them, all of the evidence to date shows that - when properly and consistently worn -  face masks (both surgical and N95/KN95) can greatly reduce your risk of infection from respiratory viruses. 

In 2022, an MMWR report found `Consistent use of a face mask or respirator in indoor public settings was associated with lower odds of a positive SARS-CoV-2 test result (adjusted odds ratio = 0.44). Use of respirators with higher filtration capacity was associated with the most protection, compared with no mask use.'

Four months ago, in JAMA Network: Masks During Pandemics Caused by Respiratory Pathogens—Evidence and Implications for Action, after presenting the available evidence, the authors wrote:

Available evidence strongly suggests that masking in the community can reduce the spread of SARS-CoV-2 and that masking with the highest-quality masks that can be made widely available should play an important role in controlling whatever pandemic caused by a respiratory pathogen awaits us.

Also last fall, we looked at a study which showed how quickly influenza and COVID rebounded in Hong Kong after their mask mandate was removed (see EID Journal: Influenza Resurgence after Relaxation of Public Health and Social Measures, Hong Kong, 2023).  

Today we've another research article, published in Frontiers of Public Health, which looks at the effectiveness of face masks in preventing influenza transmission in China; both before and during the COVID pandemic. 

One of the `downsides' to mask wearing is our natural exposure to respiratory viruses is limited, which can lead to less individual immunity over time, and a rebound in infections.  This is thought to have sparked the strong resurgence of influenza after mask mandates ended. 

While an expected side effect, its impact can probably be lessened by increased uptake of influenza (and/or pandemic) vaccines. 

Due to its length, I've only posted the abstract and some excerpts.  Follow the link to read the report in its entirety.  I'll have a postscript after the break. 

The effect of nonpharmaceutical interventions on influenza virus transmission

Danlei Chen1,2†Ting Zhang1†Simiao Chen2Xuanwen Ru2Qingyi Shao1,2Qing Ye2*Dongqing Cheng1*

Background: The use of nonpharmaceutical interventions (NPIs) during severe acute respiratory syndrome 2019 (COVID-19) outbreaks may influence the spread of influenza viruses. This study aimed to evaluate the impact of NPIs against SARS-CoV-2 on the epidemiological features of the influenza season in China.

Methods: We conducted a retrospective observational study analyzing influenza monitoring data obtained from the China National Influenza Center between 2011 and 2023. We compared the changes in influenza-positive patients in the pre-COVID-19 epidemic, during the COVID-19 epidemic, and post-COVID-19 epidemic phases to evaluate the effect of NPIs on influenza virus transmission.

Results: NPIs targeting COVID-19 significantly suppressed influenza activity in China from 2019 to 2022. In the seventh week after the implementation of the NPIs, the number of influenza-positive patients decreased by 97.46% in southern regions of China and 90.31% in northern regions of China.

However, the lifting of these policies in December 2022 led to an unprecedented surge in influenza-positive cases in autumn and winter from 2022 to 2023. The percentage of positive influenza cases increased by 206.41% (p < 0.001), with high positivity rates reported in both the northern and southern regions of China.

Conclusion: Our findings suggest that NPIs against SARS-CoV-2 are effective at controlling influenza epidemics but may compromise individuals’ immunity to the virus.

         (SNIP)         

In the past 3 years, the widespread implementation of NPIs has greatly reduced the intensity of influenza virus infections. This may be beneficial in the short term, but research shows that immunization debt may have a greater negative impact (42). From 2019 to 2022, the activity of the influenza virus will be unprecedentedly suppressed. There is insufficient immune stimulation for people infected with influenza virus. When the susceptibility of the population increases, group immunity decreases, increasing the proportion of the population vulnerable to virus infection (43). As of April 25, 2023, the national influenza detection rate was 20.92% (48,527/231918), and the highest positive rate was 55.10%. The peak stage influenza positivity rate was higher than that prior to contracting COVID-19, and the highest level of influenza positivity has occurred since 2011. The 2023 influenza season is more severe than it was in previous years, with high influenza positivity rates that will lead to mass population infections in the near term. Schools were closed in many places, and hospitals saw a multifold increase in flu patients.

In conclusion, this study revealed that the low level of influenza activity in China from 2019 to 2021 was unprecedented, possibly due to the implementation of NPIs. This discovery has been confirmed in the United States and other studies. The high level of influenza activity in China in the fall and winter of 2022–2023 is likely a result of immune debt.

We summarized our experience with the COVID-19 outbreak. We found that we should spontaneously adopt nonpharmacological interventions, such as washing hands frequently, wearing masks and reducing people’s movement. Moreover, we can increase the influenza vaccination rate to minimize the negative impact of the outbreak. The weakness of this study is that the association between age and influenza was not analyzed. Future studies could focus on analyzing the disease burden of influenza in different age groups.

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Face masks continue to be divisive, with many openly doubting their effectiveness.  

Last spring, many on social media were claiming a January Cochrane study proved that masks don't work.  But Karla Soares-Weiser, Editor-in-Chief of the Cochrane Library, issued a statement (see Cochrane Statement On Misinterpretations Of Their Mask Study) clarifying the study's findings.

Since COVID is unlikely to be the last severe pandemic threat we will face - or the deadliest - it is important that we better understand both the advantages and the limitations of wearing face masks.  

Masks aren't perfect; they can be uncomfortable or restrictive, good ones can be costly or in short supply, and they aren't 100% effective in preventing transmission. But when properly used they can be an effective protective measure until an effective vaccine can be distributed. 

Today, while supplies are abundant and prices are low, would be a good time to make sure you have an extra box or two of surgical masks, KN95s, or N95 respirators in your emergency kit. 

This was a recommendation I was making long before COVID emerged, and one I continue to make. 

Hong Kong CHP Update On H9 Influenza Investigation

   

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On Wednesday we learned of Hong Kong's 9th confirmed case of H9 influenza (see Hong Kong CHP Investigating An H9 Infection), which is the first they've seen since 2020.  Globally, a bit more than 100 cases have been confirmed (see FluTrackers list) although seroprevalence studies suggest that many cases go unreported.

Today HK's Centre for Health Protection (CHP) published the following update on their investigation, which confirms the subtype to be H9N2, reassures that no reassortment has occurred with seasonal flu, and indicates that no additional cases have been identified. 

CHP reports investigation progress of case of influenza A (H9) infection

The Centre for Health Protection (CHP) of the Department of Health (DH) today (February 23) said that, regarding the human case of influenza A (H9) infection announced earlier, the subtype of the virus infected by the 22-month-old girl was confirmed as H9N2 by the Public Health Laboratory Services Branch of the CHP.

"According to the whole genome sequencing result, it is believed that the H9N2 virus isolated from sample of the patient are of avian origin. The relevant avian influenza virus showed no re-assortment with genes of human influenza origin. The CHP also found that the relevant H9N2 virus is sensitive to antiviral medicine Tamiflu." a spokesman for the CHP said.

The symptoms of the patient had subsided and is still undergoing isolation at Princess Margaret Hospital. She is now in stable condition. Also, the CHP earlier announced that one of her home contacts had presented with upper respiratory tract infection symptoms. Her nasopharyngeal aspirate sample tested negative against influenza A virus.

The CHP has already notified the health authority of the Mainland and the World Health Organization of the case. The CHP also uploaded the aforementioned genetic sequence result to the international genomic database GISAID. Epidemiological investigation of the case is ongoing.

Novel influenza A infection, including influenza A (H9), is a notifiable infectious disease in Hong Kong. Influenza A (H9N2) infection is a mild form of avian influenza. Nine cases of influenza A (H9N2) had been reported since 1999. The recent case was an imported case reported in 2020. No deaths have been recorded so far.

A stringent surveillance mechanism by the CHP with public and private hospitals, with practising doctors and at boundary control points is firmly in place. Suspected cases will be immediately referred to public hospitals for follow-up investigation.

"Travellers, especially those returning from avian influenza-affected areas and provinces with fever or respiratory symptoms, should immediately wear masks, seek medical attention and reveal their travel history to doctors. Healthcare professionals should pay special attention to patients who might have had contact with poultry, birds or their droppings in affected areas and provinces," the spokesman advised.

Members of the public should remain vigilant and take heed of the preventive advice against avian influenza below:

• Do not visit live poultry markets. Avoid contact with poultry, birds and their droppings. If contact has been made, thoroughly wash hands with soap;
• Poultry and eggs should be thoroughly cooked before eating;
• Wash hands frequently with soap, especially before touching the mouth, nose or eyes, handling food or eating; after going to the toilet or touching public installations or equipment (including escalator handrails, elevator control panels and door knobs); or when hands are dirtied by respiratory secretions after coughing or sneezing;
• Cover the nose and mouth while sneezing or coughing, hold the spit with a tissue and put it into a covered dustbin;
• Avoid crowded places and contact with fever patients;
• Wear masks when respiratory symptoms develop or when taking care of fever patients;
• Travellers if feeling unwell when outside Hong Kong, especially if having a fever or cough, should wear a surgical mask and inform the hotel staff or tour leader and seek medical advice at once; and
• Travellers returning from affected areas with avian influenza outbreaks should consult doctors promptly if they have flu-like symptoms, and inform the doctor of the travel history and wear a surgical mask to help prevent spread of the disease.

​The public may visit the CHP's avian influenza page (www.chp.gov.hk/en/view_content/24244.html) and website (www.chp.gov.hk/files/pdf/global_statistics_avian_influenza_e.pdf) for more information on avian influenza-affected areas and provinces.

Ends/Friday, February 23, 2024
Issued at HKT 20:30

While H9N2 infection is generally mild or moderate in humans, this LPAI subtype easily reassorts with other flu viruses, making any infection a concern.   

During flu season, the possibility exists that someone could be co-infected with seasonal flu and H9N2, making it possible that a hybrid (reassortment) might emerge (see The `Other Mixing Vessel' For Pandemic Influenza).

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While the odds of that happening may be long, they are not zero.  Which is why HK's CHP is taking this investigation seriously. 

WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2024

Credit NIAID

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In addition to deciding which influenza virus components to include in the seasonal flu vaccine, twice each year flu researchers meet with the WHO to discuss the development of new CVVs (Candidate Vaccine Viruses) for zoonotic influenza. 

Just as there are a growing number subclades of seasonal H3N2 and H1N1 jockeying for dominance in the flu world (see the ECDC's Influenza virus characterization - Summary report, Europe, January 2024), there are dozens of continually evolving subclades and genotypes of avian and swine flu viruses competing in the wild.

When we speak about an avian H5 virus, or a swine H1 virus - we are actually talking about an array of genetically distinct variants - each on their own evolutionary path. And a vaccine developed against one strain of the same subtype may not prove protective against another.

Over the past 2 decades nearly 4 dozen H5Nx candidate vaccine viruses (CVVs) have been selected by WHO for development. Many of these older CVVs are for viruses that no longer circulate in the wild, having been supplanted by newer versions.

Although it can be expensive, having a proven CVV already tested and approved can save months of valuable time if mass production and distribution of a pandemic vaccine is ever required.

Today's WHO report describes recent detections of a variety of novel H5, H9, H10, and H1 flu viruses with zoonotic potential around the world, and recommendations for new CVVs. 

While no new H5, H9, or H10 CVVs were recommended, over the past six months seen a number of novel swine-origin H1 viruses emerge around the world, including Eurosurveillance: A Case of Swine Influenza A(H1N2)v in England, November 2023.

From today's report, we learn that  2 new H1 viruses have been selected for CVV development.

Influenza A(H1)v activity from 26 September 2023 to 19 February 2024

Three A(H1N1)v virus infections were identified; one each in Brazil (clade 1A.3.3.2 5 ), Spain (clade 1A.3.3.2) and Switzerland (clade 1C.2.2). The cases from Spain and Switzerland reported exposure to swine; no swine exposure was reported for the case from Brazil. The case from Brazil was severe, those from Spain and Switzerland were mild and all individuals recovered. An A(H1N2)v (clade 1B.1.1.1) virus infection was detected in the United Kingdom of Great Britain and Northern Ireland. The individual had mild disease and did not report exposure to swine.

A summary of recent A(H1) activity in swine and humans is shown in Table 4.

Genetic and antigenic characteristics of influenza A(H1)v viruses

Although virus isolation is pending or was unsuccessful from the four A(H1)v virus infections, sequence analysis showed varying levels of HA similarity to existing zoonotic CVVs or seasonal vaccine reference viruses. The A(H1)v viruses were most similar to swine viruses detected in the relevant countries or regions.

Recent clade 1A.3.3.2 viruses from swine that are genetically similar to the virus causing the human infection n Spain (A/Catalonia/NSAV198289092/2023) (Fig. 1), reacted poorly to post-infection ferret antisera raised against existing A(H1N1)pdm09 vaccine reference viruses (Table 5) and adult human sera. No CVVs for clade 1A.3.3.2 swine viruses are available.

          (SNIP)

Influenza A(H1)v candidate vaccine viruses

Based on the current genetic, antigenic, and epidemiologic data, new CVVs that are antigenically like A/Catalonia/NSAV198289092/2023 and A/England/234600203/2023 are proposed. The available and pending A(H1)v CVVs are listed in Table 7.

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Follow the link to read the full 11-page report.