Vaccine Technology

Novavax Recombinant Protein Nanoparticle Vaccine Technology –

Overview

Genetic Engineering in Sf9 Cells

Advantages of Novavax Technology

Recombinant Protein Nanoparticles:  VLPs and Micelles

Overview

Novavax has developed a platform upon which we can manufacture a variety of proprietary recombinant nanoparticle vaccines. Our proprietary platform combines the flexibility and speed of genetic engineering with the efficiency of single-use disposable technology to produce highly immunogenic nanoparticle vaccines. We are using this nanoparticle platform to develop vaccines against viral, bacterial, and parasitic diseases to address major unmet medical needs to protect against human pathogens.

Unlike traditional vaccines that are based on killed viruses or live, attenuated viruses, Novavax uses recombinant technology that allows us to customize the components of our vaccine candidates in order to solve challenges presented by novel infectious diseases. For example, in the event of a pandemic influenza threat caused by a n ew influenza strain, our scientists will be able to utilize the genetic code of the novel pandemic influenza viruses provided by the World Health Organization (WHO) and produce, in a matter of weeks, a vaccine candidate designed to generate protective immunity to specifically target that novel virus. Generally our vaccines are composed of one or more critical surface proteins of the specific virus or pathogen we are targeting. In the case of influenza, Novavax' influenza vaccines contain the important surface proteins known as hemagglutininand neuraminidase. These proteins are designed to induce immunity in the vaccine recipient, which neutralizes the virus and creates protection against further exposure to the disease.

Genetic Engineering in Sf9 Cells

Our production of vaccine nanoparticles is done in cells that were originally isolated in the 1970s from the ovaries of the fall army worm (Spodoptera frugiperda), which led to a series of "Sf" cell lines. In the early 1980s, scientists at Texas A&M (Smith, et al. 1983) discovered that one such insect cell line, called Sf9, could grow in perpetuity when in special culture media and could be made to produce recombinant proteins by infecting them with an insect virus (Baculovirus or BV) engineered to carry a foreign gene or genes of interest. The Sf9/BV genetic engineering technology is now well established in the biopharmaceutical industry. For example a licensed vaccine for Human Papilloma Virus (HPV), which showed >95% effectiveness in reducing the incidence of cervical cancer, was produced in the insect cell/BV system. More recently a Sf9/BV produced Hepatitis E vaccine candidate was evaluated in a large field trial and found to confer protective efficacy of 96%. Novavax uses Sf9/BV technology to produce a wide range of vaccine candidates derived from viruses, bacteria and protozoan parasites.

Advantages of Novavax Technology

Our manufacturing platform has a number of important advantages:

  • Our carefully designed genetic constructs allow us to focus the vaccines' immune responses on key components of pathogens, which can enhance functional immunity and lead to better prophylactic protection.
  • Sf9/BV efficiently expresses large antigens and particles, which also promote superior immunogenicity and better functional immunity.
  • Our manufacturing platform 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.

Recombinant Protein Nanoparticles:  VLPs and Micelles

Novavax' manufacturing platform produces two different types of immunogenic particles that form the basis of our vaccines: virus-like particles (or VLPs) and recombinant protein micelles.

Novavax' seasonal influenzavaccine and pandemic influenzavaccine consist of VLPs, meaning recombinant particles with matrix proteins that provide a structure onto which the surface proteins hemagglutinin and neuraminidase are incorporated. VLP constructs resemble the virus they are designed to protect against; however, because they do not contain any RNA, they are not infectious and thus are generally highly immunogenic.

Unlike VLPs, our recombinant protein micelles are generally composed of a single target protein, engineered to assemble into stable nanoparticles that elicit an immunogenic response like the virus itself. For example, our Respiratory Syncytial Virus (RSV) vaccine candidate is composed of recombinant micelles engineered as modified full-length fusion (F) proteins with the potential to induce protection against all strains of RSV. These proteins assemble into micelles with flower-like structures called rosettes.

Novavax has also produced new vaccine candidates for the prevention of SARSmalaria,andrabies. Our rabies vaccine is composed of recombinant micelles of the major surface glycoprotein in a configuration that we believe preserves the essential structure for effective immunity and creates a highly immunogenic vaccine.

Using our Sf9/BV platform, we have created a varied vaccine portfolio for both existing and novel vaccines that represent important advances over existing and future vaccines 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.