Currently marketed influenza vaccines are based on a development, production and vaccination strategy that has not changed significantly in the past five decades. Due to the seasonal nature of the disease and the genetic instability of the virus, it is necessary to formulate a new influenza vaccine each year based on an epidemiological prediction of the strains most likely to be circulating in the human population in the next winter's flu season. Current vaccines are formulated with hemagglutinin (HA) as the the viral antigen (the component of the virus, usually a protein, that serves as a target for an immune response). Due to slow development and production cycles, there is general concern that traditional vaccines may not consistently meet the demands of seasonal influenza or potential pandemic virus outbreaks.

 

The novel approach championed by VaxInnate is designed to meet those demands by drawing upon breakthroughs in our knowledge of the way the immune system works and taking advantage of efficient manufacturing technology. By leveraging the two primary mechanisms of immune defense, referred to as "innate" and "adaptive" responses, VaxInnate's proprietary TLR technology leads to a more effective vaccine against antigens. Because the vaccines can be produced as soluble biopharmaceutical grade proteins in bacteria, they can be developed and manufactured at a large scale within a short period of time.

VaxInnate lead vaccine candidates against influenza HA have been tested in the clinic demonstrating that our recombinant, soluble proteins are highly potent and well tolerated as a vaccine in both young adults and the elderly, inducing antibody responses which neutralize the influenza virus. Potency in elderly populations is especially important since this population is at greatest risk for influenza disease and is the least responsive population to the currently licensed, standard influenza vaccines on the market.

VaxInnate’s bacterial production of the influenza HA vaccine proved more efficient and cost-effective than current influenza vaccine production techniques using eggs or cell-culture. Instead, VaxInnate grows the necessary proteins in a bacterial expression system, a proven method that is commonly used in the production of other recombinant proteins and biopharmaceuticals.

VaxInnate's TLR technology is based on the ability of "toll-like receptors" (TLRs) on the cells of the innate immune system to recognize certain molecular patterns associated invading pathogens, triggering an adaptive immune response including the production of antibodies. The company's vaccines combine proteins of vaccine antigen (such as the influenza HA) and bacterial flagellin, a component of the long hair-like tails that help bacteria swim and one of the molecular patterns recognized by TLRs. Physically linking flagellin to antigens leads to a more potent vaccine than just administering a mixture of the two unattached components. The method has been demonstrated to produce robust protective immune responses in animal models to several pathogens including Dengue Virus, Japanese Encephalitis Virus and West Nile Virus, in addition to influenza. Because flagellin is a stable bacterial protein, these fusion products are simple to make using recombinant DNA techniques. The ability to rapidly develop and manufacture large quantities of the fusion product vaccines makes them ideally suited for responding to seasonal variants of influenza, or emerging pandemic viruses.

 

Current vaccine manufacturing is based on growing virus in live fertilized chicken eggs. In a laborious process, the virus is then harvested, purified and processed to recover viral antigens. Egg-based systems take six to nine months to manufacture and release a year's batch of vaccine, making it difficult to predict demand or respond quickly to public health emergencies. Mammalian cell-culture manufacturing systems for flu vaccine, while offering several advantages, are still costly and time consuming.

VaxInnate's fusion vaccine can be efficiently and economically manufactured in bacteria. The technology for producing large quantities of proteins in bacteria has been practiced for over two decades, and many currently available protein-based drugs are manufactured in this way. The method involves the insertion of a circular DNA "vector" coding for the flagellin-antigen fusion product into bacteria. The DNA directs the synthesis of the fusion product in the bacteria which then purified as soluble recombinant protein using straight forward standard biotechnology processes. Applied to vaccines, bacteria-based production avoids traditional egg- or cell culture-based manufacturing, lowers the cost of goods of the final product, and establishes a more rapidly scalable manufacturing process. In addition, a bacteria-based manufacturing process avoids the risk that an avian flu pandemic will destroy egg-laying flocks.

The immune system is composed of two arms that takes two different, yet interdependent approaches to defeating a foreign pathogen such as a bacteria or a virus.

The innate immune system. This system mounts an immediate response to an infection without being specific to the pathogen in question. The innate immune system is the more primitive of the body's responses to infection. It is made up of immune cells and receptors (including so-called 'toll-like receptors' or TLRs) that immediately recognize certain molecular patterns uniquely associated with pathogens like the bacterial protein flagellin and then launch a first-line attack on the invaders. The innate immune system then specifically presents the components of the pathogens it has recognized via TLRs to the second arm, the adaptive immune system.

The adaptive immune system. This system has the distinct advantage of highly specific recognition of virtually any pathogen the body might encounter, as well as providing immunological memory of infection. It is responsible for the production of antibodies and killer T cells. However, the adaptive system relies upon the innate systems recognition of a pathogen and its subsequent presentation to initiate its own response to a pathogen. While the adaptive systems recognition of a pathogen is extremely precise, it is relatively slow compared to the timescale of an infection.

Together, these two systems provide a comprehensive and specific immune response to infectious agents. It is precisely this biological partnership that has been harnessed to produce VaxInnate's highly specific and potent vaccines using recombinant biopharmaceutical proteins.

 

Hemagglutinin binds to sugars on the surface of host cells and helps the virus to fuse with, and enter the cell. Its essential role in the infection cycle has made HA an obvious and effective target (antigen) for traditional influenza vaccines. There is considerable genetic variance among type A virus strains, and the variants are grouped according to the particular HA sub-types present. Influenza A subtypes have designations such as H3 or H1, reflecting the identity of the particular HA proteins variants expressed by the virus subtype. Most human influenza viruses have H1 or H3 hemagglutinins, while avian influenza viral strains characteristically have H5, H7 or H9.