Novavax, Inc., the American vaccine development company, has been developing a recombinant protein nanoparticle COVID-19 vaccine currently termed NVX-CoV2373. The full-length spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is created in a baculovirus vector, which is then inserted into a lipid nanoparticle around 50 nm in diameter. Thus far, it has undergone several clinical trials and is stated to be 89% effective against SARS-CoV-2 in the UK in late January 2021. The lipid nanoparticle also contains Matrix-M1 adjuvant, which induces activation of the immune response. Including this adjuvant allows lower doses of the spike protein to be delivered and induced strong CD4+ effector memory T-cell responses.
The vaccine has shown good tolerability in those aged 18-59. In a research paper recently uploaded to the preprint server medRxiv* by Formica et al. (March 1st, 2021), the safety and toxicity profile was evaluated in older and younger individuals.
How was the trial performed?
In order to assess the suitable vaccine dosing regimen over 1,000 participants were given either one or two doses of 5 µg, 25 µg, or placebo, 21 days apart. Five roughly equal groups were generated using randomized approaches from these participants, receiving two doses of NVX-CoV2373 and Matrix-M1 in the following quantities (µg) in the first/second dose, respectively:
- 0/0 and 0/0 (placebo group)
- 5/5 and 50/50
- 5/0 and 50/0
- 25/25 and 50/50
- 25/0 and 50/0
7 days after each dose patients were asked to record any pain, tenderness, swelling, erythmia, or any other adverse effects, and based on this the reactogenicity of the vaccine was graded according to the FDA toxicity rating protocol. Additionally, the immunoglobulin G response towards the SARS-CoV-2 spike protein of those included in the study was assessed by ELISA assay, with baseline IgG measured at day 0 and recorded at days 21 and 35.
Was the vaccine effective?
Across both adult and elderly age groups, adverse events were higher in the groups receiving the vaccine than the placebo at both stages of administration, with the most common complaints being tenderness and pain. However, older participants tended to experience these side-effects to a lesser extent.
Following the first injection, there was no notable difference in more serious adverse events between placebo or vaccine-receiving groups. Following the second there was seen to be a slight rise in these cases among those receiving the vaccine, with the most common complaints being fatigue, muscle pain, headache, and malaise. Again, the frequency of these events was higher among the adult age group than the elderly. Other even more severe symptoms, such as, in one case, atrial fibrillation, were noted to be consistent across the groups and were explained by other pre-existing conditions or coincidences not related to the vaccine or COVID-19. The vaccine appears to be safe, as generally only mild side effects associated with other vaccines, such as muscle pain, are reported here.
7 days after the first dose, at day 21, younger participants receiving 5 to 25 µg NVX-CoV2373 had a 12-25 fold rise relative to baseline anti-spike IgG titers, while older participants had only a 4-8 fold rise. The approximately halved response of older participants is expected due to immunosenescence and may go some way to explaining the lesser-reporting of adverse side effects from this group.
At day 35, 7 days after the second dose, anti-spike IgG titers were 386 and 385 fold relative to baseline in those receiving two doses of 5 µg or 25 µg NVX-CoV2373, respectively.
The dose quantity at first vaccination demonstrated no apparent difference between those receiving 5 or 25 µg NVX-CoV2373, both producing similar neutralizing antibody responses and adverse effects. Similarly, each second vaccine dose size produced comparable seroconversion rates with high IgG levels, though the higher of the doses demonstrated more intense local and systemic reactogenicity.
The Matrix-M1 adjuvanted NVX-CoV2373 vaccine seems to be highly immunogenic and well-tolerated in a wide range of individuals, though clinical trials continue.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults Neil Formica, Raburn Mallory, Gary Albert, Michelle Robinson, Joyce S. Plested, Iksung Cho, Andreana Robertson, Filip Dubovsky, Gregory M. Glenn, for the 2019nCoV-101 Study Group, medRxiv, 2021.02.26.21252482; doi: https://doi.org/10.1101/2021.02.26.21252482, https://www.medrxiv.org/content/10.1101/2021.02.26.21252482v1