Results of a phase 2 trial of the Novavax reconstituted SARS-CoV-2 nanoparticle vaccine

Novavax, Inc., the American vaccine development company, has been developing a COVID-19 nanoparticle protein recycling vaccine called NVX-CoV2373. The full-length spike protein of respiratory respiratory syndrome coronavirus 2 (SARS-CoV-2) is formed in a baculovirus vector, which is then implanted into a lipid nanoparticle approximately 50 nm in diameter . To date, it has undergone several clinical trials and is said to be 89% effective against SARS-CoV-2 in the UK at the end of January 2021. The lipid nanoparticle also contains Matrix-M1 receptor, which causes activation of the immune response. The introduction of this enhancer allows lower doses of the spike protein and the introduction of potent T-cell memory responses of CD4 + effect.

The vaccine has shown good tolerance in those aged 18-59. In a research paper recently uploaded to the preprint server medRxiv * and Formica et al. (March 1^st, 2021), safety and toxicity profile were assessed in older and younger individuals.

How was the trial conducted?

To evaluate the appropriate vaccine dose regimen, more than 1,000 participants received one or two doses of 5 µg, 25 µg, or placebo, 21 days apart. Five roughly identical groups were created using randomized methods from these participants, obtaining two doses of NVX-CoV2373 and Matrix-M1 in the following sizes (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 pain, tenderness, swelling, erythmia, or any other side effects, and based on this the reaction of the vaccine was assessed according to the FDA toxic rating protocol. In addition, the immunoglobulin G response to SARS-CoV-2 spike proteins of those included in the study was assessed by an 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 placebo at all 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.

After the first injection, there was no significant difference in worsening adverse events between placebo or vaccinated groups. After the second there was a small increase in these cases among those receiving the vaccine, with the most common complaints being obesity, muscle pain, headache and malaise. Again, the frequency of these events was higher among the adult age group than the elderly. Even more severe symptoms, such as, in one case, atrial fibrillation, were identified as consistent across the groups and were explained by other conditions or comorbidities not related to the vaccine or COVID-19. The vaccine appears to be safe, as only minor side effects associated with other vaccines, such as muscle pain, are generally 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 increase compared with baseline anti-spike IgG titers, while and older participants had only a 4–8 fold increase. The response is expected in about half of older participants as a result of immunosenescence and may go a little further in explaining the lesser reported adverse effect from this group.

At day 35, 7 days after the second dose, anti-spike IgG titers 386 and 385 were folded compared to baseline in those receiving two doses of 5 µg or 25 µg NVX-CoV2373, separately.

The dose dose at the first vaccine showed no difference between those receiving 5 or 25 µg NVX-CoV2373, both producing similar neutral antibody responses and adverse effects. Similarly, every second dose of vaccine produced comparable seroconversion levels with high IgG levels, although the highest dose increases indicated more intense local and systemic reactogenicity.

The matrix-enhanced NVX-CoV2373 vaccine Matrix-M1 appears to be highly protective and patient in a wide range of humans, although clinical trials are ongoing.

* Important message

medRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.