Our recombinant, protein-based nanoparticle vaccine technology

Vaccines can take years or even decades to develop. Our vaccine technology combines the power and speed of genetic engineering to efficiently produce protein-based nanoparticles.

These protein-based nanoparticles work with our proprietary Matrix-M™ adjuvant, which helps to enhance immunogenicity—ie, the ability of the vaccine to provoke an immune response in the body.

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Our nanoparticle vaccine and adjuvant platform can be used to rapidly create investigational vaccines for existing and new pathogens, helping the world address important global health threats.

A brief history of vaccines: standing on the shoulders of historical successes

Vaccination has been used to control certain diseases since the late 18th century, when Edward Jenner used matter from cowpox lesions to inoculate people against smallpox.1 Since then, as understanding and technology have progressed, vaccination has become a key method to help prevent the transmission of some infectious diseases. In fact, only access to clean water has a greater positive impact on global health than vaccinations.2

Older vaccines, such as those successful against measles and polio, use a dead or weakened (attenuated) pathogen to activate the body’s immune system and stimulate antibody production. However, in someone with a compromised immune system, an attenuated pathogen may still cause the disease, and a dead pathogen may not result in a strong enough or long-lasting immune response.3 Thankfully, vaccine development has progressed.

Over recent decades, protein-based vaccines have been developed and successfully used to help combat infectious diseases such as diphtheria and tetanus. Instead of using the whole pathogen, these vaccines use a specific protein from the pathogen (known as an antigen), which has no function on its own but can be recognized by the body’s immune system.4 When isolated, purified, and injected into the body, this protein-based vaccine can provoke an immune response to help protect the body from infection without causing the disease.3

Through further scientific advances, the processes used to develop these protein-based vaccines have improved, making it quicker and easier to identify the best antigen for use in the vaccine and to produce this material in the quantities required.

One process that is crucial to the production of many vaccines, including ours, is genetic engineering. This technique enables Novavax scientists to use the genetic material from target pathogens to create highly purified recombinant proteins.5,6

Novavax' vaccine development: from established genetic engineering to unique nanoparticle

Creating a recombinant protein is only the first step in producing a Novavax vaccine. In our vaccines, we organize recombinant proteins in a nanoparticle. This arrangement mimics nature, helping your immune system recognize that target protein from different angles7—the same way that your immune system would see the details of a real pathogen. In our vaccines, there’s no actual virus, just the protein. The vaccines can’t cause disease.

Learning to recognize vaccine proteins in this way helps train your immune system to develop protective antibodies that can help prevent you from getting sick.8,9

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Novavax vaccine technology in action: fighting COVID-19

COVID-19 is caused by the SARS-CoV-2 virus. The virus uses a protein on its surface, known as the spike protein, to attach itself to human cells and cause infection.10 Novavax makes a protein that precisely mimics the virus’ version of the spike protein. In our vaccine, we organize spike proteins into a nanoparticle to help your immune system recognize the target spike. Learning to recognize the spike proteins in this way helps your immune system protect you from getting sick from COVID-19.

Nanoparticles with spike proteins are just 1 of 2 important parts of the Novavax vaccine. The spike protein is the “signal,” but to generate immunity that may help protect you from COVID-19, we want your immune system to hear that signal loud and clear.

That signal boost comes from our Matrix-M “adjuvant.” Tiny Matrix-M adjuvant particles increase the activity of your immune system when you receive a vaccine.7,11 Together, the vaccine’s spike protein and Matrix-M adjuvant help stimulate a protective immune response.

Three regions of the earth with hotspots indicating amount of infected areas. Pandemic. Epidemic. Endemic.

On their own, the vaccine’s spike protein nanoparticles are not enough to trigger a full immune response, so we mix them with our proprietary Matrix-M adjuvant to help produce a stronger immune signal with the aim of protecting immunity.12

6 steps to producing a Novavax investigational vaccine13:

  1. After identifying an antigen that can be used to stimulate an immune response against the virus in question, the corresponding gene is modified and inserted into a baculovirus (a type of insect virus).
  2. The baculovirus containing the recombinant antigen gene is used to infect cells from a certain type of moth (called Sf9 cells); the baculovirus multiplies (replicates) inside these cells.
  3. As part of this replication process, the recombinant antigen gene from the baculovirus enters the Sf9 cell nucleus where it is transcribed into mRNA.
  4. The natural machinery in the Sf9 cells translates the mRNA to produce large quantities of the recombinant antigen protein.
  5. The recombinant antigen proteins are harvested from the surface of the Sf9 cells, purified, and arranged around a nanoparticle core.
  6. The recombinant antigen protein nanoparticles are mixed with the Matrix-M adjuvant to create the investigational vaccine.

Our vaccine technology: disease-agnostic and adaptable

Novavax’ vaccine technology is adaptable. As the SARS-CoV-2 virus evolves, for example, our vaccine can be adjusted to use the version of the spike protein found in new variants.

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Recombinant, protein-based nanoparticle designed to immunize against the original strain

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Recombinant, protein-based nanoparticle designed to immunize against a variant strain

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If a new SARS-CoV-2 variant appears and our vaccine does not provide sufficient protection, the genetic sequence of the new variant is used to produce a new version of the recombinant spike protein. We use the same approach to producing and testing an investigational vaccine that is specific to that new virus variant.

Our approach to vaccines also can be applied to other pathogens, using nanoparticle technology to combat threats such as influenza and Ebola.

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We are also working on combining more than one type of protein-based nanoparticle into a single vaccine candidate to help provide coverage for 2 or more strains of the same virus. Our nanoparticle technology is now also being used to combine antigens from different pathogens to help immunize against more than 1 disease with a single vaccine.

One example of how we are doing this is by studying the combination of seasonal influenza with SARS-CoV-2 in 1 investigational vaccine. This may allow us to help individuals to protect themselves against both the flu and COVID-19 through a single vaccination.

Combination vaccines

Novavax' vaccine technology enables us to combine multiple types of vaccine nanoparticles into a single, ready-to-use vaccine. Combination vaccines reduce the number of shots required to protect against multiple diseases. Simplifying immunizations into fewer shots may make it more likely that people get recommended vaccinations on time, reducing delays in protection.14,15

Novavax is developing an investigational combination vaccine to simultaneously combat both influenza and SARS-CoV-2. The vaccine uses the full-length, stabilized, recombinant spike (rS) protein of the SARS-CoV-2 virus, and 4 wild-type recombinant hemagglutinin (rHA) proteins from the influenza virus as antigens. Antigens are organized into distinct nanoparticle complexes recognized by the immune system.

Preclinical trials in animals have shown that a single shot of the combined vaccine successfully generated antibodies against both viruses at comparable levels to using either vaccine alone.16 Novavax has launched a phase 1/2 trial to evaluate the safety and immunogenicity of this investigational combination vaccine.

  1. Riedel S. Proc (Bayl Univ Med Cent). 2005;18(1):21–25.
  2. Vaccination greatly reduces disease, disability, death and inequity worldwide. Bull World Health Organ. 2008;86:140–146.
  3. How Vaccines Work. Public Health. Available at https://www.publichealth.org/public-awareness/understanding-vaccines/vaccines-work/ [Accessed 3 Sept 2021].
  4. Vaccine Types. NIH 2019. Available at https://www.niaid.nih.gov/research/vaccine-types [Accessed 3 Sept 2021].
  5. McCullers JA, Dun JD. PT. 2008;33:35–41.
  6. Nascimiento IP, Leite LCC. Braz J Med Biol Res. 2012;45:1102–1111.
  7. Krueger S, et al. Mol Pharm. 2021;18(1):359–376.
  8. Gorman M, et al. August 2021. Available at https://doi.org/10.1016/j.xcrm.2021.100405 [Accessed 2 Feb 2022].
  9. Tian J-H, et al. Nat Commun. 2021;12:372.
  10. Bangaru S, et al. Science. 2020;370:1089–1094.
  11. Keech C, et al. N Engl J Med. 2020;383(24):2320–2332.
  12. How to produce a Novavax vaccine. 2021. Data on File.
  13. Chow EJ, et al. Crit Care. 2019;23:214.
  14. Combination Vaccines. CDC. August 2019. Available at https://www.cdc.gov/vaccines/parents/schedules/combination-vaccines.html [Accessed 2 Feb 2022].
  15. Skibinski D, et al. J Glob Infect Dis. 2011;3(1):63-72. doi:10.4103/0974-777X.77298.
  16. Massare MJ, et al. Combination Respiratory Vaccine Containing Recombinant SARS-CoV-2 Spike and Quadrivalent Seasonal Influenza Hemagglutinin Nanoparticles with Matrix-M Adjuvant. bioRxiv. Preprint posted online May 5, 2021. doi: 10.1101/2021.05.05.442782.
Additional reading

Additional reading

The mixture of our recombinant, protein-based nanoparticles and our proprietary Matrix-M adjuvant is aimed to help provide robust and functional immunity.

Matrix-M adjuvant technology

Check out our pipeline to find out more about what we are working on and how we’re aiming to help change the future of certain infectious diseases.

Our pipeline—creating tomorrow's vaccines today