What do we know about the Novavax vaccine? – Expert Q&A

The Novavax vaccine is the remaining Covid-19 jab among the Government’s pre-purchase agreements that’s under review by Medsafe, with doses expected to arrive early next year.

Medicines regulator Medsafe approved the three other vaccines in the Government’s Covid-19 vaccine portfolio this year, with only the Pfizer/BioNTech vaccine currently being used in New Zealand’s vaccination campaign.

The SMC asked experts to comment on how the Novavax vaccine works and its safety profile.

Dr Fran Priddy, Executive Director Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, comments:

How does the Novavax vaccine work? How is it different from the other three New Zealand-approved vaccines?

“The Novavax COVID-19 vaccine (NVX-CoV2372) is a protein-based vaccine. Protein-based vaccines have a good safety and efficacy track record and are used in adults and children to prevent diseases such as hepatitis B, pertussis, influenza, pneumococcal illness and meningitis. They are typically given together with an adjuvant to boost the immune response and ensure both humoral (antibody) and cellular (T cells) responses. The Novavax vaccine is made from multiple copies of the SARS CoV-2 spike protein, formed into tiny particles (nanoparticles) and then mixed together with an adjuvant derived from tree bark. It is given as an intramuscular jab like other COVID-19 vaccines, with two doses given three weeks apart.  After injection, the nanoparticles are taken up antigen presenting cells, which then display the spike proteins on their surface and stimulate the immune system to make antibodies and cellular responses.”

What do the data show so far about its effectiveness and safety?

“The Novavax COVID-19 vaccine had a good safety profile and was 90 per cent effective in preventing symptomatic COVID-19 disease and 100 per cent protective against hospitalisation and death in large clinical trials in the UK, US and Mexico. These trials were conducted prior to widespread prevalence of the Delta variant. There is no data on efficacy against the Delta variant yet, but lab testing showed that vaccinees have immune responses that also neutralise the Delta variant. In a study of people vaccinated with the Novavax as their primary series and then boosted with a third dose 6 months later, neutralizing responses to the Delta variant increased more than four-fold.”

What is known about its potential use as a booster to the Pfizer vaccine?

“There are two studies ongoing in the UK looking at several different regimens, including using Novavax with the Pfizer vaccine. One study includes an evaluation of people who received one dose of Pfizer vaccine and a second dose with the Novavax vaccine as their primary series. The second study is evaluating people who received both doses of Pfizer vaccine as their primary series and then a booster with Novavax full dose, or Novavax at half-dose. Both studies are evaluating safety and immune responses, and the data is expected in the very near future.”

Conflict of interest statement: Dr Priddy is Executive Director of the Government-funded Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, a partnership between the Malaghan Institute, the University of Otago and Victoria University of Wellington. She is Clinical Evaluation Director at Malaghan Institute.

Professor Peter McIntyre, Medical Advisor, Immunisation Advisory Centre, comments:

“There has been some recent interest in the Novavax COVID-19 vaccine candidate, which is one of the vaccines for which New Zealand has expressed interest. I cannot comment on what may be under consideration with respect to booster doses. However, I am not aware of any strong reasons to consider Novavax over other candidate vaccines for use as a booster should this be endorsed in the future. In general, use of the same vaccine for the whole course is recommended, although studies have and will be examining mixed schedules of different vaccine types, including their use as boosters – more of that later.”

What is the Novavax vaccine?

“Unlike some other COVID-19 vaccines being used widely worldwide – mRNA vaccines (Pfizer/Moderna) and adenoviral vector vaccines (Janssen/AstraZeneca), which use totally new platforms – Novavax uses a variation of a traditional vaccine approach with a long history of use. This is where a protein (which is part of the causative organism) is used to stimulate protective antibody. Other vaccines based on a protein include tetanus and diphtheria (where a modified version of the toxin produced by the bug is used), pertussis and hepatitis B (where a part of the organism is used), and most recently the new zoster vaccine (Shingrix, which is not yet marketed in New Zealand).”

How does the Novavax vaccine differ from other protein vaccines?

“Mainly in the way the spike protein in the vaccine is produced but also in the adjuvant which is added to the vaccine to make stronger immune responses.

Production: a virus (baculovirus), which does not infect humans, is engineered to contain a gene encoding full-length SARS-CoV-2 spike glycoprotein and then the baculovirus put into insect cells (in this case from a moth), which it infects. This way of producing a vaccine via baculovirus and insect cells is also used by the Cervarix HPV vaccine, which has been used in many millions of doses worldwide.

“Inside the moth cells, the baculovirus produces lots of spike protein, which is extracted from the cell culture and added to a sugar (polysorbate 80 [PS 80]), which allows it to be assembled into very small nanoparticles. The nanoparticles are basically parcels of spike protein that can enter muscle cells more easily when injected as a vaccine. The nanoparticle approach looks promising – it was used in an RSV vaccine trialled in New Zealand about five years ago and is also being used for an influenza vaccine.

Adjuvant: A special adjuvant (Matrix-M1) is bonded to the nanoparticles. Adjuvants are substances that do not produce an immune response themselves, but when added to a vaccine, boost the body’s immune response to it. The oldest example (aluminium) has been used in vaccines like tetanus for over 70 years. The Matrix adjuvant is a much more potent immune stimulant than aluminium. It is made from a soap-like complex sugar (saponin) that comes from the bark of a tree – some lipid is added to this so it can combine with the protein nanoparticles. The matrix adjuvant very strongly boosts immune responses – the adjuvant used in the Shingrix zoster vaccine also uses an adjuvant containing saponin and over six million doses of Shingrix have been given in the US. The strong adjuvant means that even people over 80 years of age who typically have weak responses to vaccines respond well.”

How has it performed in clinical trials?

“In trials to date, the Novavax vaccine has been shown to be effective in preventing SARS-CoV-2 infections in both the UK and South Africa. Although its performance in South Africa (efficacy ~ 55%) was not as good as in UK (~90%) against any infection with symptoms, when just moderate or severe infections were looked at there were none in the vaccine group in either South Africa or UK, whereas there were 14 in the placebo group (100% against moderate or severe disease).

“There is no data specifically for protection against the Delta strain, which was not circulating at the time of the trials; laboratory studies suggest that the vaccine would provide protection and the company has announced that when given as a third (booster) dose, the antibody levels against Delta are particularly high.”

What do the data show so far about its safety?

“No safety signals of concern have been seen in trials so far. Rare but previously unsuspected safety issues like clotting with low platelets (adenovirus vector vaccines) or myocarditis (mRNA vaccines), which turned up when millions of people had received these vaccines would not be expected, because new aspects of the Novavax manufacture (baculovirus, saponin adjuvant) have been used in millions of people in other vaccines with no problems and the basic approach of using a protein directly injected is used in many other vaccines.

“As a result, it may be more acceptable to people who are concerned about ‘new’ technologies and also be useful as a second dose in people who have had reactions to mRNA or adenovirus vector vaccines.”

What is known about its potential use as a booster to the Pfizer vaccine?

“Could it be used down the track in people who have already had something else? Very likely, but ideally would like real data on what happens when you do this – a trial that will include Novavax as a second dose after one dose of AstraZeneca or Pfizer, or as a booster after two doses of Pfizer, is currently underway in the UK.”

Where has the vaccine been approved?

“The vaccine is under review by Medsafe and other agencies around the world – it has not yet been given emergency use approval anywhere, but this is anticipated soon. Then it is a matter of when supplies would be available for use by which time more data will be available.”

No conflicts of interest declared. NOTE: The Immunisation Advisory Centre (IMAC) has a contract with the Ministry of Health to delivery education and training to the healthcare sector for COVID-19 vaccines.