EXPERT REACTION: Novavax becomes fourth COVID-19 vaccine provisionally approved by TGA

We have been very fortunate in this country to have three safe and effective vaccines using two different platforms in use for some time, and the high uptake of these vaccines in addition to other mitigation strategies has put us in an enviable position in this pandemic even despite seeing intense community transmission right now due to the Omicron variant.

For a variety of reasons, it seems some have remained reluctant to receive these vaccines thus far so an additional option, based on what is considered perhaps a more traditional platform, is likely to increase our vaccination rate even further.

Today it's exciting to hear that Novavax has been approved for use in Australia. This vaccine started its clinical trial journey in Australia, and I was fortunate to be the Principal Investigator on that study that administered this vaccine to healthy volunteers for the first time on the 26th of May 2020.

Following the success of this study, this vaccine was then subsequently studied intensively in large clinical trials around the world that demonstrated an efficacy rate above 90 per cent and a favourable safety profile.

This is a protein-based vaccine, the first to be approved for COVID-19 in Australia, given as two doses three weeks apart. It is now approved for individuals 18 years of age or older as a primary vaccination, however there are many ongoing clinical trials including using as a booster, in younger people and even in combination with influenza vaccines.

Another significant favourable property of this vaccine is that it can be stored for nine months at standard refrigeration temperatures. While there’s no question the vaccine rate in this country has been impressive, we still need to strive to increase uptake and having this vaccine, one that is based on a different platform to those already available, should mean we now have the ability to do so and ideally do so quickly. 

Novavax is a protein subunit vaccine. That means they fabricate the non-infection component on the surface of the coronavirus, manufacture that, and build the components of the vaccine that create an immune response.
 
Some people have been hesitant about receiving vaccines created on mRNA or adenovirus platforms, so Novavax as a protein subunit vaccine could offer an alternative for them. 
 
Phase 1 and 2 studies of the Novavax vaccine were done in Australia, and efficacy was found to be greater than 90 per cent. 
 
The reported side effects of Novavax seem to be minor, in line with other protein recombinant vaccines – such as the Hepatitis B vaccine which has been widely used in Australia for years.
 
Novavax also has potential to become part of Australia’s booster plan in the future. It’s my understanding that results of studies of the vaccine for children over 12 and adolescents, and results of the booster studies, will be available for TGA approval within the next couple of months.

The TGA has approved the Novavax vaccine and two oral pills for use in Australia. A small percentage of vaccine hesitant people around the world including in Australia were holding out for a vaccine built from purified proteins.

Unlike the relatively new technologies that the mRNA vaccines (used in Pfizer and Moderna vaccine) and viral-vector COVID-19 vaccine (used in Astra Zeneca), protein vaccines have been used for decades to protect people from hepatitis, shingles, and other viral infections. To elicit a protective immune response, these vaccines deliver proteins, along with immunity-stimulating adjuvants, directly to a person’s cells, rather than a fragment of genetic code that the cells must read to synthesise the proteins. 

It is predicted that protein vaccines will play an important part in COVID-19 vaccines over time, because of their track record in safety and efficacy and they have demonstrated strong protection with fewer side effects. The vaccines have been approved in November 2021 in the UK and Indonesia and in December 2021 in the US.

What is not publicised is that home-grown protein-based vaccines have been produced in Cuba which has administered the COVID-19 vaccine to its population with strong vaccine uptake. Taiwan has also done the same with its national vaccine which is protein based. India and China are in the advanced stages of producing protein-based COVID-19 vaccines.

The approval of Novavax and other protein-based vaccines will help to fill a void in the global pandemic response. We know that there is significant vaccine inequity in the world with less than 10 per cent of people in low and middle income countries (LMICs) vaccinated against COVID-19. Protein-based vaccines have inexpensive production protocols and logistical advantages, including stability at a range of temperatures and will help to narrow the immunisation gap between rich and poor countries. We hope these vaccines will reach vulnerable populations in LMICs.

It is important that another vaccine in our ability to protect against SARS CoV-2 has recently been provisionally approved by the TGA.

Of note, the approval is for use as a two dose primary course in adults (aged 18 years and over). Australia already has high vaccine coverage for the primary course, with two dose coverage in adults at >92 per cent. There will be a small group of people who were reluctant to get the mRNA or adenoviral vector vaccine, who may now go and get the Novavax vaccine - as it is a protein based vaccine, similar in design to other non COVID-19 vaccines in use in Australia.

The key will be whether the vaccine is approved by the TGA for use as a booster, given the already high vaccine coverage in adults for the primary series - there is no approval for this use at present. A recent publication in the Lancet by Munro et al - demonstrated that Novavax as a booster after both Pfizer and AstraZeneca primary course was safe and elicited a boost in antibody levels.  During the current Omicron wave it is clear that a booster dose improves your protection.

We know that all COVID-19 vaccines teach the immune system how to recognize the virus and prepare the body to mount an attack.

The Novavax vaccine (Nuvaxovid) is a protein subunit vaccine. It uses a harmless piece of the spike protein from the coronavirus that causes COVID-19 to stimulate and prepare the immune system for future encounters with the virus.

How does it work?

Nuvaxovid works by preparing the body to defend itself against COVID-19. It contains a version of the spike protein that has been produced in the laboratory. It also contains an ‘adjuvant’, a substance to help strengthen the immune responses to the vaccine.

When a person is given the vaccine, their immune system will identify the protein in the vaccine as foreign and produce natural defences - antibodies and T cells - against it. If, later on, the vaccinated person comes into contact with the SARS-CoV-2 virus, the immune system will recognise the spike protein on the virus and be prepared to attack it.

The antibodies and immune cells can protect against COVID-19 by working together to kill the virus, prevent its entry into the body’s cells, and destroy infected cells.

How is it different from current mRNA and adenoviral vector vaccines?

Unlike the relatively new technologies that the mRNA and viral-vector COVID-19 shots are based on, protein vaccines have been used for decades to protect people from hepatitis, shingles and other viral infections. To elicit a protective immune response, these shots deliver proteins, along with immunity-stimulating adjuvants, directly to a person’s cells, rather than a fragment of genetic code that the cells must read to synthesize the proteins themselves.

What are the potential benefits?

Protein-based vaccines - with their inexpensive production protocols and logistical advantages, including stability at a broad range of temperatures - could help to narrow the immunisation gap between rich and poor countries. Apart from that, this vaccine can be produced at a much larger scale because appropriate manufacturing facilities are already available in comparison with a more complex system for the mRNA vaccines, for example.

It can be a potential game changer to people who refuse vaccinations due to rare potential side effects from the mRNA vaccines (Pfizer, Moderna) and Adenoviral vectored vaccines (AstraZeneca, J&J, Sputnik V) such as myocarditis and blood clots.

What is the efficacy of this protein-based vaccine?

The efficacy of Nuvaxovid has been assessed in three Phase 2 and Phase 3 trials. Of the two Phase 3 trials, both found that the efficacy of the vaccine against mild, moderate, and severe disease is 90 per cent. In addition to that, in a Phase 3 study conducted in the USA and Mexico during a period in which multiple variants (Alpha, Beta and Delta) were in circulation, vaccine efficacy against mild, moderate, or severe COVID-19 was 90 per cent. There are currently limited data whether this vaccine prevents transmission and infection and its protection against Omicron with studies still being conducted.