Nuvaxovid (Novavax) COVID-19 vaccine

Immunogenicity

Pre-clinical trials of Nuvaxovid (Novavax) were conducted in baboons and mice. In animal models, the vaccine induced high levels of anti-spike antibodies and neutralising antibodies, which exceeded the responses measured in humans recovered from natural COVID-19 infection.

Phase 1 clinical trials were conducted in 131 healthy adults aged 18-59 years in Australia and the United States of America (USA). The study assessed the safety and immunogenicity of two doses (low dose 5-μg and high dose 25-μg) with or without Matrix-M1 adjuvant in healthy adults aged 18 to 59 years, compared to a placebo. Overall the vaccine elicited a good immune response, with immunogenicity comparable in both low and high dose groups. An enhanced immune response was seen in the adjuvant group.

A phase 2 trial in Australia and the USA expanded the age of participants to include 1,288 participants aged 18-84. Results of this study indicated that a two-dose regimen of 5-µg NVX-CoV2373 administered 21 days apart was the optimal vaccine dose to proceed to phase 3 trials.

Safety profile

Side effects following administration of Nuvaxovid (Novavax) have been generally mild to moderate, and short-lived. Injection site pain and tenderness, as well as fatigue, headache and muscle pain were the most commonly reported side effects, particularly after dose 2, and more commonly in younger recipients (18-64 years). The incidence of serious adverse events was low and reported in similar numbers in both the vaccine arm and placebo group. Three cases of myocarditis were reported in the phase III clinical trials, two of which were in the vaccine arm and one in the placebo group.

Vaccine efficacy

United Kingdom (UK)

Phase 3 clinical trials in the UK enrolled more than 15,000 participants aged between 18-84 years of age. Overall efficacy of 89.7% against PCR confirmed disease was demonstrated 7 days following receipt of dose 2.  It was 96.4% efficacious against the original COVID-19 strain and 86.3% against the circulating Alpha strain. There was 100% protection against severe disease (hospitalisation and death) for both strains.

South Africa

A phase 2b clinical trial  conducted in South Africa included 4387 participants (HIV-negative and HIV-positive). The vaccine demonstrated 49.4% efficacy in preventing COVID-19 disease caused by the Beta variant for all participants. This increased to 60.1% efficacy for the HIV-negative only cohort. All COVID-19 infections in the vaccine group were mild/moderate, and there were no severe cases. Serious adverse events were rare and unrelated to the vaccine.

United States of America (USA)

Approximately 30,000 participants were enrolled in PREVENT-19 (PRE-fusion protein subunit Vaccine Efficacy Novavax Trial COVID-19), a phase 3 trial in Mexico and the USA. The vaccine demonstrated 90.4% efficacy overall for preventing symptomatic COVID-19 disease, with 100% protection against moderate and severe disease. For “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure) the vaccine was reported to be 91.0% efficacious.

Further studies

Paediatric clinical trials

Children were not included in the initial Novavax COVID-19 vaccines clinical trials due to the decrease in severity of symptoms experienced by children infected with SARS-CoV-2 compared with infected adults. Various clinical trials are currently underway to determine the safety and efficacy of Nuvaxovid (Novavax) in the paediatric population (12-17 years).

For further information refer to MVEC: COVID-19 vaccination in children.

Clinical trial crossover

In April 2021, Novavax announced that they would introduce crossover arms for all three trials in the UK, South Africa and USA. Participants in the UK and the US who were given the placebo in the initial trial will now be offered the active vaccine. In South Africa all participants will be offered the active vaccine, meaning that those who previously received the placebo will be vaccinated and those who received the vaccine previously will receive a booster dose. This will give all participants the opportunity to receive protection with ongoing follow up. All participants will remain blinded.

Booster study

From December 2021, an extension of the PREVENT-19 phase 3 clinical trial commenced. Participants will be offered a booster dose of Nuvaxovid 6 months following the completion of their primary course. The safety and efficacy of a booster dose of Nuvaxovid administered in two other groups will also be assessed (those who received alternate brands of COVID-19 vaccine as the initial course and those who only received 1 dose of Nuvaxovid as their primary course).

Resources

• TGA: Provisional approval for Nuvaxovid (Novavax NVX-CoV273)
• ATAGI statement on the use of Novavax COVID-19 vaccine (Nuvaxovid)
• NEJM: Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
• PLOS One: Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccines (NVX-CoV2373) in younger and older adults
• NEJM: Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine
• NEJM: Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant
• National Institutes of Health: U.S. clinical trial results show Novavax vaccine is safe and prevents COVID-19