Influenza (flu) is a respiratory infection in mammals and birds. It is caused by an RNA virus in the family Orthomyxoviridae. The virus is divided into three main types (Influenza A, Influenza B, and Influenza C), which are distinguished by differences in two major internal proteins (hemagglutinin (HA) and neuraminidase (NA)). Influenza virus type A is found in a wide variety of bird and mammal species and can undergo major shifts in immunological properties. Influenza B is largely confined to humans and is an important cause of morbidity. Little is known about Influenza C, which is not an important source of morbidity.
Influenza A is further divided into subtypes based on differences in the membrane proteins hemagglutinin (HA) and neuraminidase (NA), which are the most important targets for the immune system. The notation HhNn is used to refer to the subtype comprising the hth discovered Hemagglutinin (HA) protein and the nth discovered neuraminidase (NA) protein. Influenza viruses that are known to infect human include the following sub-types. H1N1 virus that caused "Spanish Flu" (A/BrevigMission/1/1918(H1N1)) and seasonal flu (A/Brisbane/59/2007(H1N1), A/New Caledonia/20/1999(H1N1), and A/Solomon Islands/3/2006 (H1N1)) and a reassorted virus (A/California/04/2009(H1N1)) that caused the 2009 swine flu outbreak; H2N2 virus that caused the "Asian Flu"; H3N2 virus that caused the "Hong Kong Flu"; H5N1 "The Bird Flu" virus (A/Anhui/1/2005 (H5N1), A/Vietnam/1203/2004, A/Vietnam/1194/2004 (H5N1), A/bar-headed goose/Qinghai/14/2008 (H5N1), A/turkey/1/2005 (H5N1), A/Indonesia/5/2005 (H5N1)) that was the world's major influenza pandemic threat until the Swine Flu Pandemic of 2009; H7N7 virus that has unusual zoonotic potential; H1N2 is currently endemic in humans and pigs; and H9N2, H7N2, H7N3, H10N7 viruses.
The influenza viral Hemagglutinin (HA) protein is a homo trimer with a receptor binding pocket on the globular head of each monomer, and the influenza viral neuraminidase (NA) protein is a tetramer with an enzyme active site on the head of each monomer. Subtypes are further divided into strains; each genetically distinct virus isolate is usually considered to be a separate strain.
The influenza virus Hemagglutinin (HA) protein is translated in cells as a single protein, HA0, or hemagglutinin precursor protein. For viral activation, hemagglutinin precursor protein (HA0) must be cleaved by a trypsin-like serine endoprotease at a specific site, normally coded for by a single basic amino acid (usually arginine) between the HA1 and HA2 domains of the protein. After cleavage, the two disulfide-bonded protein domains produce the mature form of the protein subunits as a prerequisite for the conformational change necessary for fusion and hence viral infectivity.
The influenza virus neuraminidase (NA) protein is a second major surface antigen of the virion. Neuraminidase (NA) cleaves terminal sialic acid from glycoproteins or glycolipids. Thus, it functions to free virus particles from host cell receptors, to permit progeny virions to escape from the cell in which they arose, and so facilitate virus spread.
On April 29th 2009, the World Health Organization (WHO) announced that the rapid global spread of a new swine origin strain of influenza A (H1N1) virus (A/California/04/2009 (H1N1), A/California/06/2009 (H1N1), A/California/07/2009 (H1N1)) detected in the previous week warranted moving the global flu pandemic alert level to phase 5. Phase 5 indicates sustained human-to-human transmission of a novel influenza strain of animal origin in one WHO region of the world, and exported cases detected in other regions. Since its outbreak, the new swine influenza H1N1 virus has infected millions of people worldwide and hundreds of death. This new influenza outbreak is commonly referred to as the 2009 swine flu pandemic.
The highly pathogenic H5N1 avian influenza virus has become endemic in poultry in southeast Asia since 2003 and constitutes a major pandemic threat to humans. During 2004, H5N1 virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry.
Influenza virus vaccination is an effective approach to control influenza virus infection and pandemic spread of the virus. Each seasonal influenza vaccine contains hemagglutinin (HA) and neuraminidase antigen from three influenza subtype viruses-one subtype Influenza A H3N2 virus, one regular seasonal Influenza A H1N1 virus (not the 2009 H1N1 virus), and one Influenza B virus. Because of the influenza virus continues to mutate (antigen minor drifting or antigen major shifting) over time, the viruses in the vaccine change each year based on international surveillance and scientists' estimations about which types and strains of viruses will circulate in a given year. About 2 weeks after vaccination of the influenza viral antigen, antibodies that provide protection against influenza virus infection develop in the body.
Seasonal influenza virus vaccines are manufactured with a 50-year old egg-based process technology. Virus seed is injected into fertilized chicken eggs and incubated for several days to allow the virus to replicate and accumulate in the fluid surrounding the embryo. The virus fluid is collected from the inoculated eggs and harvested, purified, chemically inactivated and used to produce the vaccine.
Protection mechanism of influenza vaccine is well established to be neutralizing antibody (polyclonal human antibody) raised against influenza viral protein antigen such as the hemagglutinin (HA ) and neuraminidase (NA) protein antigen. Neutralizing antibody can block virus binding to host cells, block viral entry into host cells, and kill infected host cells. Recombinant monoclonal antibody (Mab, mouse monoclonal antibody, rabbit monoclonal antibody, chimeric monoclonal antibody, humanized monoclonal antibody) raised against the hemagglutinin (HA ) antigen or cloned from human B-cells (human monoclonal antibody) have shown to be promising anti-influenza infection product candidates.
Monoclonal or polyclonal antibody can be raised with peptide based antigen or protein based antigen. Antibody raised with protein based antigen could have better specificity and/or binding affinity than antibody raised with peptide based antigen, but cost associated with the recombinant protein antigen is usually higher. Anti influenza virus hemagglutinin (HA) monoclonal antibody or polyclonal antibody can be used for ELISA assay, western blotting detection, Immunohistochemistry (IHC), flow cytometry, neutralization assay, hemagglutinin inhibition assay, and early diagnosis of influenza viral infection.
Sino Biological is committed to use its expertise in recombinant protein and antibody development to provide solutions to support the influenza research community worldwide. Our solutions include contract service, recombinant hemagglutinin (HA) protein reagent, mouse and rabbit anti-hemagglutinin (HA) monoclonal antibody, anti-hemagglutinin (HA) polyclonal antibody, H1N1 hemagglutinin (HA) antibody pair (dual-set) for ELISA assay. All of our monoclonal or polyclonal antibody reagents are generated from immunization with recombinant hemagglutinin (HA) protein antigen, and hence should have better specificity and affinity than antibody raised from peptide based antigen. We are committed to develop innovative and cost-effective solutions. More influenza related protein and antibody reagents are coming.