Research on Zoonotic (Animal Origin) Influenza (Flu) Viruses of Public Health Concern

What are zoonotic flu viruses of public health concern?

Flu viruses of public health concern include the following:

• Novel (i.e., non-human) flu viruses of zoonotic (animal origin) that have caused past human infections. For example, Asian lineage highly pathogenic avian influenza (HPAI)* A(H5N1) or Asian lineage A(H7N9) viruses are zoonotic flu viruses of public health concern because they have infected people and caused serious illness.
• Zoonotic origin flu viruses that have not caused past human infection(s) but that may have the potential to cause human infections. For example, the HPAI A(H5) viruses identified in the United States in 2015 have not caused human infections but remain flu viruses of public health concern because of their potential to cause human illness.

A common characteristic of all zoonotic flu viruses of public health concern is that most people do not have pre-existing antibodies or immune protection against them.

*Avian influenza A viruses are designated as highly pathogenic avian influenza (HPAI) or low pathogenicity avian influenza (LPAI) based on molecular characteristics of the virus and the ability of the virus to cause disease and mortality in chickens in a laboratory setting.

Why does CDC conduct research on zoonotic flu viruses of public health concern?

CDC conducts research on flu viruses of public health concern because most humans do not have any pre-existing immunity against them, and should these viruses gain the ability to spread efficiently among humans, they could cause a global outbreak of disease, i.e., a pandemic.

Flu viruses constantly change (see antigenic drift and shift, and sometimes these changes result in the emergence of a novel flu virus that can easily infect and spread between people. CDC Influenza Division is a World Health Organization (WHO) Collaborating Centre for Influenza. In this role, CDC conducts surveillance of seasonal flu viruses circulating in people to make informed decisions on the selection of viruses for use in creating seasonal flu vaccines. As part of CDC’s role as a WHO Collaborating Centre for Influenza,  CDC also receives zoonotic viruses of public health concern that CDC characterizes and uses to create candidate vaccine viruses (CVVs) that can be used to produce vaccines against viruses with pandemic potential. CDC also conducts research on zoonotic flu viruses of public health concern to learn more about these viruses. For example, CDC studies where these viruses spread, how they spread, who gets infections, and what kinds of illness they cause. This information can help scientists better understand the risk these viruses pose to humans and support development of tools and strategies for prevention and treatment.

The two flu viruses of public health concern that have caused the most human infections are both bird flu viruses: “Asian lineage avian influenza (HPAI) A(H5N1) and Asian lineage A(H7N9) viruses. These two viruses have caused severe illness and death in humans.

What is the purpose of this research?

CDC conducts laboratory research on zoonotic flu viruses of public health concern for important reasons, including but not limited to the following:

• to develop candidate vaccine viruses (CVVs) for use in vaccines as part of pandemic preparedness efforts;
• to test to see if flu viruses of public health concern are susceptible (sensitive) or resistant to existing flu antiviral drugs, and to monitor for ongoing changes that might indicate these viruses are becoming resistant;
• to develop diagnostic tests and test materials that can accurately and reliably detect human infections with specific zoonotic flu viruses of public health concern, such as Asian lineage A(H5N1) and Asian lineage A(H7N9) bird flu viruses;
• to assess existing human immunity to zoonotic flu viruses of public health concern and to determine whether people’s previous vaccinations or exposures to other flu viruses provides cross-protection against these flu viruses;
• to better understand properties of zoonotic flu viruses of public health concern and changes in these flu viruses (mutations) that could cause such viruses to infect people more easily, cause more severe disease, or spread in a sustained and efficient manner among people or other mammals;
• to track globally where novel flu viruses are causing illness in people so that appropriate public health precautions and actions can be taken to minimize risks to the public’s health in those areas.

What research does CDC conduct on zoonotic flu viruses of public health concern?

CDC conducts laboratory tests on zoonotic flu viruses of public health concern including, but not limited to the following: antigenic characterization, antiviral resistance, genetic characterization, serology and assessment of flu viruses’ ability to cause disease and spread in animal models. See below for a more detailed explanation of each of these laboratory tests.

Genetic Characterization

Genetic characterization as it applies to flu research is the study of the genes of a flu virus using a laboratory process known as “genome sequencing.” Through genome sequencing researchers can determine the order of the amino acids that form the proteins of a flu virus. Comparing the order of amino acids in one sequence to other sequences can reveal variations that might impact characteristics of the flu virus. For example, the composition of these amino acids can affect factors such as how well a virus replicates during infection, how well it transmits between hosts, its similarity or “match” to current available vaccines, and susceptibility to vaccines and its susceptibility to treatment with antiviral drugs. Flu researchers use genetic characterization to better understand these markers and to assess the risk these viruses pose to public health. Nearly all flu virus samples submitted to CDC undergo genetic sequencing as a first step in the process of studying the virus.

Antigenic Characterization

“Antigenic characterization” is the analysis of a flu virus’ surface features using antibodies. CDC researchers determine a flu virus’ antigenic (immune) properties to help assess how related different flu viruses are to each other. CDC flu laboratorians conduct antigenic characterization as part of global flu surveillance efforts to measure possible changes in circulating zoonotic flu viruses, such as bird flu viruses. If antigenic characterization shows that stockpiled vaccines no longer offer protection against newer viruses of public health concern, then health officials can decide to develop new vaccines. In some circumstances, CDC prepares candidate vaccine viruses in advance that vaccine manufacturers can use to produce a flu vaccine in the future, should it be needed. The main test used to conduct antigenic characterization is the hemagglutination inhibition assay (HI test). CDC primarily conducts antigenic characterization on bird flu H5, H7, and H9 viruses, but may test other types of flu viruses that pose a potential risk to humans. More information on antigenic characterization is available on CDC’s flu antigenic characterization page.

Antiviral Resistance Testing

Virus are tested to determine if they are resistant to any of the FDA-approved flu antiviral drugs. This information helps shape public health policy recommendations on the use of flu antiviral medications. CDC currently recommends use of the neuraminidase inhibitor class of antiviral drugs to prevent and treat flu illness in the United States. The neuraminidase inhibitors are drugs designed to bind to the neuraminidase protein on the surface of a flu virus to prevent the virus from replicating in the host. (More information about flu antiviral drugs is available at Treatment – Antiviral Drugs.) Antiviral resistance testing includes sequencing as well as a specific functional assay, the neuraminidase inhibition (NI) assay, to see whether virus replication is inhibited by the presence of the neuraminidase drugs.

Serology

Serology is the study of blood serum. Serum contains antibodies, which are proteins produced by the body in response to infection or vaccination. Antibodies play an essential role in protection against flu viruses. CDC’s flu serology research involves the study of antibodies in human populations to better understand whether people have any existing protection against different flu viruses. These studies can tell public health officials whether people in the study population are susceptible to infection with a particular virus or if they have existing immune protection against infection. This information is important for determining a virus’ pandemic potential or ability to spread through a population. In addition, serology is used to determine whether vaccines developed against specific flu viruses are likely to offer adequate protection and whether this protection is likely to be effective against newly emerging flu viruses.

Animal testing

CDC conducts animal studies using zoonotic flu viruses of public health concern to better understand these viruses, such as how transmissible they are in mammals, their disease severity and disease characteristics, and to test the efficacy of vaccines and other pharmaceutical interventions against them.

How has CDC research helped to improve testing for zoonotic flu viruses of public health concern, such as bird flu?

CDC research has strengthened the ability of the United States and foreign countries to detect zoonotic flu viruses of public health concern. For example, in February 2006 and September 2008 the U.S. Food and Drug Administration (FDA) cleared new CDC developed molecular laboratory tests to aid in the diagnosis of Asian A(H5N1) bird flu viruses in human respiratory specimens. CDC has since expanded its molecular test kits to detect other flu viruses, such as Asian A(H7N9) bird flu virus, which began causing human infections in China in 2013. CDC’s test kits have been made available to state public health laboratories and have been shared globally with World Health Organization (WHO) collaborating centers and international influenza testing centers.

What is “dual use research of concern (DURC)?”

Some types of flu research that are beneficial to society also fall into a category called “dual use research of concern” (DURC). DURC is defined as life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be potentially misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. More information about DURC is available at Dual Use Research of Concern and Bird Flu: Questions & Answers.