In 2009, the emergence of the novel H1N1 influenza virus demonstrated how quickly a flu pandemic can sweep across the world. Recent data shows seasonal influenza causes up to 646,000 deaths globally each year, with approximately 36,000 fatalities in the U.S. Although vaccination is an effective method to prevent influenza infection, viral diversity is the primary challenge for developing a broadly protective influenza vaccine. Vaccines with broad specificity and relatively streamlined production are critically needed to control future influenza outbreaks. Although some vaccines exist currently for H1N1 and H5N1, a major issue with these available products is a lack of broad coverage of different viral clades due to virus diversity. The H5N1 vaccine is also ineffective in controlling the variations of clades in H5N1 responsible for human infections. It has a costly and time-consuming development process and can lead to hypersensitivity reactions among patients.
Description
Pitt researchers have found a solution by developing a recombinant tetravalent HA-DBV vaccine, which holds potential for broad efficacy in the prevention of influenza. The HA-DBV vaccine simultaneously displays immunogenic proteins derived from four subclades of H5N1 influenza viruses. It offers robust protection against influenza infection in vivo, generating both cellular and humoral immune responses. To generate their candidates, investigators assessed the efficiency of a computationally optimized influenza hemagglutinin (HA) protein. They found that the signal peptide (SP) and cytoplasmic tail (CT) domains of gp64 can enhance the display of HA, while the transmembrane domain of gp64 impairs HA display. By constructing a recombinant proteins, researchers discovered a method that computationally optimizes the influenza HA protein to generate immunity against a broad range of clades within each influenza subtype, including H1N1, H3N2, H2N2, and B influenza. This technology generates HA sequences with high immunogenic activity that results in cross-reactive immune responses to all viruses tested using a single HA sequence. The discovery suggests both humoral and cellular immunity are robustly generated against a broad range of influenza clades. Scientists and researchers are developing additional vaccines using this same computational method, which may lead to vaccine development for other infectious diseases.
Applications
• Patients in the U.S. and globally seeking protection from all influenza strains
• Scientists and researchers developing additional vaccines using this same computational method
• Vaccine development for other infectious diseases
Advantages
· HA antigen uses a computational approach to prevent influenza virus infection in human, swine, and avian species
· Low dose of current vaccine can provide strong immune responses
· Vaccine may provide cross protection by stimulating humoral immune and cellular immune responses
· Offers cost reduction as insect cells can grow well in serum free medium
· Technology can be applied to other vaccines
· One universal sequence protects against any subtypes of influenza virus prevalent that year
· Vaccine production is efficient and does not require inoculation of eggs
· No need for inactivation of the virus, which can weaken the immune response and subsequent protection
Invention Readiness
In vivo, in vitro
IP Status
https://patents.google.com/patent/US10098946B2;
https://patents.google.com/patent/US9309290B2;
https://patents.google.com/patent/US10179805B2;
https://patents.google.com/patent/US9234008B2;
https://patents.google.com/patent/US9212207B2
