Novavax is a leading innovator of recombinant vaccines. Novavax scientists are capitalizing on the tools of genetic engineering and the proven baculovirus/insect expression system to solve major vaccine challenges towards addressing major urgent unmet medical needs. This is well-illustrated by the Novavax program to address respiratory syncytial virus (RSV) disease, a leading cause of infant and elderly hospitalization, which has been stymied despite 60 years of research by vaccinologists in the attempt to make a vaccine. Our scientific breakthrough in the development of an RSV nanoparticle vaccine candidate and our rapid advances in clinical development are excellent examples of the power of our technology.
Genetic Engineering in Insect Cells
Our production of vaccine nanoparticles is done in cells that were originally isolated in the 1970s from the ovaries of the fall armyworm (Spodoptera frugiperda), which led to a series of “Sf” insect cell lines. In the early 1980s, scientists at Texas A&M (Smith, et al. 1983) discovered that one such insect cell line could grow in apparent perpetuity in a special culture media and could be made to produce recombinant proteins by infecting them with a virus (baculovirus or BV, a virus that infects only insects) engineered to carry one or more foreign genes of interest. These insect cells are then “programed” (infected) with engineered BV to efficiently produce the desired protein or proteins that, unlike simple bacteria or yeast-cell expression technology, are typically correctly folded and biologically active when made in these more highly evolved insect cell lines. Novavax has developed this powerful recombinant platform based on insect cell lines and advanced engineering of genes, to be cloned into BV, to produce two different types of immunogenic nanoparticles that form the basis of our vaccine candidates:
- Virus-like particles (or VLPs), which are recombinant particles with viral matrix proteins that provide a structure onto which multiple immunogenic surface proteins can be incorporated, and,
- Recombinant protein nanoparticles, which are recombinant protein micelles generally composed of a multitude of a specific single-target protein, engineered to assemble into stable nanoparticles.
Our RSV vaccine candidate illustrates how Novavax scientists use our insect cell/BV recombinant platform to create new product candidates. Our process starts with the identification of a specific surface protein that has favorable immunogenic properties. In this case, the RSV virus has an important surface protein central to the disease process known as the fusion protein (F-protein). Our scientists isolated the genetic sequence of the F-protein and employed sophisticated recombinant genetic techniques to clone that gene into the BV. The engineered BV is then used to infect the insect cells. Upon infection, the BV utilizes the insect cell’s internal synthetic machinery to make proteins using the genetic sequence for the RSV F-protein. The Insect Cells will start producing recombinant RSV F-proteins, which undergo a series of programed modifications, folding, and ultimately transport to the cell surface. Correctly modified and folded RSV F-proteins can be extracted from the cell surfaces and fully and gently purified to maintain their three-dimensional structure and biological activity, ultimately serving as the immunogenic molecule in our vaccine. In the native RSV virus, the F-protein is unstable and does not appear to induce fully protective immune responses, however Novavax scientists designed and tailored solutions into the genetic sequence to address these problems. Additionally, our scientists devised a way for recombinant F-proteins to self-assemble into RSV F-protein nanoparticle constructs that approximate the size of the RSV virus, a strategy that has been shown to enhance immune response. We believe this recombinant vaccine engineering approach provides robust and functional immunity, and can be applied to essentially all viral, bacterial and parasitic diseases.
Another example of the power of Novavax’ Insect Cell/BV platform is our ability to produce influenza virus like particles (VLPs) using the same techniques. However, instead of producing single-target protein nanoparticles, as with our RSV vaccine, Novavax scientists incorporated the gene sequences of multiple immunogenic proteins, together with universal matrix assembly proteins, to produce more complex envelope particle vaccines. Our influenza VLP vaccines incorporate the gene sequences of the strain specific hemagglutinin (HA) and neuraminidase (NA) surface proteins. When expressed, these proteins self-assemble and bud off the insect cell. The resulting highly immunogenic entities are spherical structures roughly the same size as influenza viruses, with a lipid bilayer membrane expressing the HA and NA proteins on the surface, stabilized by the matrix assembly protein. There is no genetic material (DNA or RNA) in the VLPs therefore it is impossible for these VLPs to infect host cells and cause disease.
The insect cell/BV recombinant platform is well-established in the biopharmaceutical industry and is the basis for several licensed biologic products and vaccines. For example a licensed vaccine for Human Papilloma Virus (HPV), which showed >95% effectiveness in reducing the incidence of cervical cancer, is produced in the insect cell/BV system. Novavax can use its insect cell/BV technology to produce a wide range of vaccine candidates derived from viruses, bacteria and protozoan parasites.
Advantages of Novavax Manufacturing Technology
Our manufacturing platform has a number of important advantages:
- Our carefully designed genetic constructs allow us to focus our vaccines' immune responses on key components of pathogens, which we believe enhances functional immunity and leads to better protection against infection and disease.
- Insect cell/BV platform efficiently expresses large antigens and particles, which in turn promote superior immunogenicity and better functional immunity.
- Our manufacturing platform generally produces proteins that are properly folded, which can be critical for functional, protective immunity.
- Unlike traditional influenza vaccine manufacturing, we do not need to grow an actual influenza virus, obtain embryonated chicken eggs, and adapt the virus or optimize new strains to grow in eggs.
- Our vaccines are produced using single-use disposable manufacturing technology that accelerates process validation and analytical testing and, we believe, may allow for ultimate regulatory approval of our vaccines derived from a common platform.
Using our insect cell/BV recombinant platform, we have created a vaccine portfolio of novel vaccines that represent important advances over existing vaccines or that address currently unmet medical needs, to prevent human infectious diseases. Novavax' innovation brings an immunologic advantage, embodied by presentation of antigen as highly immunogenic particles in their native configuration, and sound principles of development, as a scalable, efficient recombinant vaccine production system.