2nd International Conference on Influenza September 12-13, 2016 Berlin, Germany

Influenza virus is introduced into the airways by aerosol or by contact with saliva or other respiratory secretions from an infected individual, it binds to and replicates in epithelial cells of both the upper and lower respiratory tract. Viral replication combined with the immune response to infection lead to destruction and loss of the epithelial cells the respiratory mucosa. Cough and weakness may persist for up to 2 weeks after infection. Influenza enters the host through the airways. Influenza complications of the upper and lower respiratory tract are common. These include otitis media, sinusitis, bronchitis, and croup. Pneumonia is among the more severe complications of influenza infection, an event most frequently observed in children or adults. Human influenza leads to complex cytopathic effects due to downregulation of host cell protein synthesis and apoptosis, predominantly in the the airways epithelial cells. Apoptosis is mediated by both Fas-mediated mechanisms and Fas-independent signals, which initiates a caspase cascade. NA can activate latent TGF-β on the cell surface by facilitating cleavage of TGF-β into its active form that up-regulates pro-apoptotic genes. Apoptosis occurs also in lymphocytes explaining the lymphopenia observed during acute infection.

There are three types of influenza virus :  A, B, and C. Type A and type B  viruses are responsible for the seasonal outbreaks of influenza. Type A flu viruses are found in many different animals, including ducks, chickens, pigs, and horses. Influenza B viruses circulate widely only among humans. Influenza viruses are constantly changing, with new strains appearing regularly. If someone had influenza in the past, their body has already made antibodies to fight that particular strain of the virus. If future influenza viruses are similar to those encountered previously, either by having the disease or by vaccination, those antibodies may prevent infection or lessen its severity. Complications of influenza can include bacterial pneumonia, ear infections, sinus infections, dehydration, and worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes.  But antibodies against flu viruses encountered in the past can't protect from new influenza subtypes that can be very different immunologically from previously infection.

The majority of the currently available licensed seasonal influenza vaccines are prepared using eggs for the following vaccine types. However, some manufacturers employ cell culture for the production of their vaccines.

• Whole virus vaccines consisting of inactivated viruses.
• Split virus vaccines consisting of inactivated virus particles disrupted by detergent treatment.
• Subunit or surface antigen vaccines consisting essentially of purified hemagglutinin and neuraminidase from which other virus components have been removed.
• Live attenuated (cold-adapted) virus vaccines consisting of weakened (non-pathogenic) whole virus.

To produce the split virus and subunit vaccines the whole virus is subjected to disruption with a surfactant, which solubilizes the viral membrane. For subunit vaccines the internal subviral core of the virus is separated from the surface proteins on the basis of their differing sedimentation rates. With split virus vaccines, the choice and use of surfactant ensures that the subviral core itself is disassembled.

Annual influenza vaccine is the best way to reduce your chances of getting the seasonal flu and spreading it to others. Vaccines work by spurring the immune system into action. The effectiveness of a vaccine depends on how vigorously the immune system responds to it. If someone have a weak immune system to begin with, a vaccine may just not work as well. Many chronic illnesses can weaken a body’s defenses.  The vaccines are generally safe. In children fever occurs in between 5 to 10%, as may muscle pains or feeling tired. In certain years, the vaccine causes Guillain Barre syndrome in older people in about one per million doses. It should not be given to those with severe allergies to eggs or to previous versions of the vaccine. They come in both inactive and weakened viral forms. The inactive version should be used those who are pregnant. They come in forms that are injected into a muscle, sprayed into the nose, or injected into the middle layer of the skin.

Outbreaks of influenza occur every year and typically reach epidemic levels at some part of the season. Antiviral drugs are a second line of defense system against influenza infection. Antiviral drugs are recommended for both treatment and prevention of flu. Antiviral drugs work best when taken within 48 hours of onset of flu symptoms, but they may still offer benefits when taken later. These medications may reduce the duration of flu by one to two days and prevent severe flu complications. The antiviral drugs have been approved for treatment of acute uncomplicated influenza and for some preventive uses. Tamiflu (oseltamivir phosphate), Relenza (zanamivir) and Rapivab (peramivir) are the three FDA-approved influenza antiviral drugs recommended by CDC for use against recently circulating influenza viruses. The effect of specific antiviral strategies in serious or life-threatening influenza is not established from clinical trials conducted to support licensure of oral oseltamivir, inhaled zanamivir, or intravenous peramivir.

Laboratory diagnosis of influenza has become a cornerstone of the prevention, containment, surveillance, and treatment of the associated illness. A number of flu tests are available to detect influenza viruses. The most common are called rapid influenza diagnostic tests. These tests can provide results in 30 minutes or less. The laboratory diagnosis of influenza uses a wide range of techniques including rapid immunoassays, immunofluorescence techniques, virus culture methods, and increasingly sophisticated molecular assays. Laboratory identification of human influenza virus infections is commonly performed using direct antigen detection, virus isolation in cell culture, or detection of influenza-specific RNA by reverse transcriptase-polymerase chain reaction (RT-PCR).

New high-throughput methods in biology are producing new patterns which would not be detectable without systematic and automated approaches because of the volume and often noisy nature of the data. data  at  an  unprecedented  rate. The  influenza  surveillance  and  vaccine  strain  selection processes are in a good position to take advantage of these new  methods. Human influenza is a complex pathogen, mostly because of its capacity to vary its surface proteins to escape immune surveillance. There are two main patterns of change. The first, antigenic shift, is the result of a new influenza A subtype  entering  the  human  population,  either  directly  or The second, antigenic drift, is the result of changes in existing human influenza viruses, to  escape  immune  surveillance indirectly  from  birds. Mathematical techniques have been used to identify clusters  in  genetic  data.

Innate and adaptive immune responses are stimulated when the influenza virus infects the cells of the respiratory tract. The innate immune response develops very quickly and controls virus replication during the early stages of infection. Innate immune system recognizes virus-infected cells through mechanisms that are not antigen-specific, the cytokines produced during this early phase of the host's defense do facilitate activation of subsequent antigen-specific adaptive immune mechanisms. Transition from the innate to the adaptive immune response is the stimulation of Toll-like receptors (TLRs) in endosomes of antigen-presenting cells (primarily dendritic cells).  TLRs recognize and bind to structural components such as single-stranded viral RNA, which are shared by different pathogens, and are important triggers of the danger signal. Stimulation of immunological memory from prior exposure to viral antigens also stimulates specific pathways in the adaptive immune response. Stimulation of immunological memory accelerates the adaptive response, which is delayed during a primary exposure to the antigen. A major aspect of the adaptive immune response involves virus binding to immunoglobulin receptors on B lymphocytes, which subsequently differentiate to plasma cells that produce virus-specific antibodies.

Influenza causes an acute infection of the host and initiates a cascade of immune reactions activating almost all parts of the immune defense system. Most of the initial innate response, including cytokine release (IFNα/β), influx of neutrophil granulocytes or natural killer cells, and cell activation, is responsible for the acute onset of the clinical symptoms. Innate immunity is an essential prerequisite for the adaptive immune response, firstly, to limit the initial viral replication and antigen load, and secondly, because the antigen-specific lymphocytes of the adaptive immune response are activated by co-stimulatory molecules that are induced on cells of the innate immune system during their interaction with viruses. Influenza viruses, however, encode in the non-structural protein 1 (NS1) mechanisms to evade and antagonize the IFN α/β response. NS1 is likely to sequester viral dsRNA which prevents recognition of this dangerous molecule by cellular sensors which would otherwise trigger IFN α/β release.

Novel introductions of influenza viruses into the human population from the animal kingdom continue to be a major health problem worldwide. The disease associated with infection shows a broad range of symptoms, depending in part on the genetic properties of the virus but also on which species of host is infected. In the natural host, no signs of infection can be identified by ocular inspection, while other bird species and mammals are more severely affected with symptoms ranging from very mild to very severe and ultimately death. It is widely accepted that all influenza virus strains infecting mammalian species originate from wild birds. Influenza A virus causes a wide spectrum of symptoms in reared birds, from mild illness to a highly contagious and fatal disease resulting in severe epidemics. Only subtypes H1N1 and H3N2 of influenza A virus follow an epidemiological pattern in humans and are considered endemic, though a H2N2 persisted for a long time. Influenza A viruses can be isolated somewhere in the world every month and the infection is sustained and perpetuated in the human population.

Currently, gene therapy refers to the transfer of a gene that encodes a functional protein into a cell or the transfer of an entity that will alter the expression of an endogenous gene in a cell. The efficient transfer of the genetic material into a cell is necessary to achieve the desired therapeutic effect. Based on the virus life cycle, infectious virions are very efficient at transferring genetic information. Most gene therapy experiments have used viral vectors comprising elements of a virus that result in a replication-incompetent virus. In initial studies, immediate or immediate early genes were deleted. These vectors could potentially undergo recombination to produce a wild-type virus capable of multiple rounds of replication. These viral vectors replaced one or more viral genes with a promoter and coding sequence of interest. Competent replicating viral vectors were produced using packaging cells that provided deleted viral genes in trans. For these viruses, protein(s) normally present on the surface of the wild-type virus were also present in the viral vector particle. Thus, the species and the cell types infected by these viral vectors remained the same as the wild-type virus from which they were derived.

Globally, influenza activity has decreased from its peak of influenza activity. The WHO’s Global Influenza Programme (GIP) provides global standards for influenza surveillance. In addition GIP collects and analyses virological and epidemiological influenza surveillance data from around the world. The regular sharing of quality influenza surveillance and monitoring data by countries allows WHO to: provide countries, areas and territories with information about influenza transmission in other parts of the world to allow national policy makers to better prepare for upcoming seasons; describe critical features of influenza epidemiology including risk groups, transmission characteristics, and impact; monitor global trends in influenza transmission; and support the selection of influenza strains for vaccine production.

Influenza vaccines and antiviral drugs business development: comprises a number of tasks and processes generally aiming at developing and implementing growth opportunities within and between organizations. It is a subset of the fields of business, commerce and organizational theory.