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Editors CornerAvian Influenza, a global threat

Avian Influenza, a global threat

Are we all prepared, or just some countries?

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Enrique Chacon Cruz, Felicitas Colombo, Javier Casellas, Vaccine, Vaccines, Vaccines Beat, Vaccinesbeat

The COVID-19 pandemic revealed our society’s vulnerability to a novel pathogen capable of causing a potentially devastating pandemic. Accordingly, global preparedness is essential.

Since November 2022, a new approach by the World Health Organization (WHO) has been implemented that focuses on entire classes of viruses and bacteria rather than individual pathogens. Over 200 scientists from 53 countries are independently evaluating evidence related to 30 viral families, one core group of bacteria, and “Pathogen X” – an unknown pathogen with the potential to trigger a severe global pandemic..

Avian influenza (AI) is currently one of the virus groups capable of causing a new pandemic.

Influenza A viruses (IAVs) are adapted to infect a wide array of hosts, spanning divergent taxonomic groups, and hundreds of birds and mammal species, including humans. Despite an expansive host range, the genetic constellation for the vast majority of antigenic mutations of IAs occur in the gut of aquatic/migratory birds and is primarily hosted by two highly divergent avian orders: Anseriformes (e.g. ducks, geese, swans) and Charadriiformes (e.g. gulls, plovers, skimmers).

Avian influenza viruses (AIVs) represent significant challenges to global public health systems due to their widespread circulation and considerable mortality rates. AIVs, which belong to the influenza A genus, have an eight segment genome and encode at least 11 different proteins, including hemagglutinin (HA) and neuraminidase (NA) glycoproteins. HA and NA in avian species are classified into 16 and 9 subtypes, respectively. These two proteins divide and determine distinct serotypes of AIV based on their genetic variations.

Highly Pathogenic and Low Pathogenic AIVs:

  • Low Pathogenic Avian Influenza (LPAI): Mostly cause either no signs of disease or mild disease in chickens/poultry (such as ruffled feathers and a drop in egg production), however, can mutate into highly pathogenic avian influenza viruses.
  • Highly Pathogenic Avian Influenza (HPAI): Cause severe disease and high mortality in infected poultry. Only some avian influenza A(H5) and A(H7) viruses are classified as HPAI A viruses, while most A(H5) and A(H7) viruses circulating among birds are LPAI A viruses.

Although AIVs A(H5), A(H6), A(H7), A(H9), and A(H10) have been proven to infect humans, A(H5N1) and A(H7N9) account for the majority of cases. However, other strains such as A(H5N2), A(H6N1), A(H10N3), A(H10N7), A(H10N8), and A(H7N2) have also been reported in recent years, raising concerns about an increasing rate of mutations.

Globally, almost 2,000 cases of AI have been reported in humans. Since 2003, over 23 countries have reported more than 880 human infections with A(H5N1) to the WHO. Although human-to-human transmission of AIVs is extremely rare, the lethality can exceed 50%. Additionally, human cases have originated not only from poultry but also from other animals, such as cows, with four cases reported in the US this year. Accordingly, the fear of mutagenic changes enhancing both human-to-human and other mammals-to-human transmission has raised concerns about a potentially disastrous pandemic.

Actions to be taken:

  • Surveillance based on the status quo situation:

1. Anticipation: Conduct viral/molecular surveillance in wild animals, particularly migratory birds.

2. Primary Prevention: Prevent spillover by reducing deforestation and climate change. Vaccination in humans at high risk.

3. Early Detection in Emergence Scenarios: Implement syndromic surveillance through clinicians and healthcare practitioners (HCPs).

4. Containment of Localized Transmission: Use epidemiologic surveillance for contact tracing.

5. Control and Mitigation in Case of an Epidemic: Scale up healthcare services (hospitals, intensive care units, primary care), enforce large-scale quarantine, and close businesses and schools as needed.

6. Pandemic Response: Implement all measures mentioned in step 5 but on a global scale.

  • Vaccination:

For Influenza, vaccination remains the most effective strategy for prevention and control in humans, despite varying vaccine efficacy across strains. However, the highly diverse mutagenic nature of AIVs makes this task particularly challenging. Current ongoing trials for AI vaccine platforms include live attenuated, inactivated, virus-like particles (VLPs), and mRNA vaccines, particularly targeting AH5N1, AH7N9, and AH9N2.

For all vaccine candidates, comprehensive quality assessments (gene sequence verification, impurity testing, exclusivity testing, trypsin assay testing, embryo lethality testing, and antigenic characterization) and determination of attenuation (pathogenicity testing in chickens and ferrets) are mandatory before initiating phase 1 clinical trials in humans.

The Food and Drug Administration (FDA) has approved three AI vaccines. As of June 2024, the U.S. has ordered 4.8 million doses of a cell-based, adjuvanted A(H5) vaccine for avian flu preparedness. Additionally, even without a single case of human AI, the government of Finland has started vaccinating high-risk individuals, and 15 European Union countries have secured 40 million doses.

Inequity, the never-ending problem:

While developed countries are implementing primary measures to prevent an AI pandemic, including large-scale molecular surveillance, upgrading healthcare facilities, and manufacturing and administering vaccines, many other parts of the world face budget constraints that prevent investment in potential threats like this disease. If AI spreads easily among humans, people in developing nations will suffer the most. However, as with COVID-19, the more industrialized world will inevitably be affected, potentially repeating the same story.

BIBLIOGRAPHY:

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Enrique Chacon Cruz, Felicitas Colombo, Javier Casellas, Vaccine, Vaccines, Vaccines Beat, Vaccinesbeat

Disclaimer:

The views and opinions expressed in this newsletter are those of the authors and do not necessarily reflect the views or positions of AHF, its sponsors, partners or any entity related to Vaccines Beat.

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