V17/USA/Covid-19 Vaccine NVX-CoV2373 / SARS-CoV-2 Vaccine NVX-CoV2373
Ending COVID
Covid-19 Vaccine NVX-CoV2373 USA
This was a trial for the COVID or rSARS-CoV-2 nanoparticle vaccine referred to as NVX-CoV2373. It was initiated on May 26, 2020 and completed on June 6, 2020. All 134 participants underwent randomization between May 27 and June 6, 2020. All 131 participants received their first vaccination on day 0, and all but 3 received their second vaccination by at least 21 days later in the month of June, 2020.
This was a randomized, placebo-controlled, phase 1–2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-μg and 25-μg doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults younger than 60 years of age.
NVX-CoV2373 is a recombinant severe acute respiratory syndrome CoV-2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.
During Phase 1, vaccination comprised of two intramuscular injections, 21 days apart. All 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo.
No serious adverse events were noted.
At 35 days, the NVX-CoV2373 vaccine appeared to be safe.
NVX-CoV2373 elicited immune responses that exceeded levels in Covid-19 convalescent serum.
The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype.
Primary immunogenicity outcome was the anti-spike IgG ELISA unit responses to rSARS-CoV-2 protein antigens, measured on days 0, 7, 21, 28, and 35. Reported secondary immunogenicity assessments were the wild-type virus microneutralization assay (MN) with an inhibitory concentration of >99% (MN IC>99%) on days 0, 21, and 35 and intracellular cytokine staining of antigen-specific CD4+ T cells at days 0 and 28 in a randomly selected subgroup of 16 participants, 4 participants each from groups A, B, C, and D.
No serious adverse events or adverse events of special interest were reported, and vaccination pause rules were not implemented.
Neutralizing Antibodies
After the first vaccination (day 21), GMFRs were approximately 5 times greater with adjuvant (5.2, 6.3, and 5.9 for groups C, D, and E, respectively) than without adjuvant (1.1). By day 35, second vaccinations with adjuvant induced an increase more than 100 times greater (195 and 165 for groups C and D, respectively) than single vaccinations without adjuvant.
The primary safety and immunogenicity analyses indicate that in healthy adult participants 18 to 59 years of age, two-dose regimens of 5 μg and 25 μg of rSARS-CoV-2 plus the Matrix-M1 adjuvant had acceptable safety findings and induced high immune responses, with levels of neutralizing antibodies that closely correlated with anti-spike IgG.
Reflected that NVX-CoV2373 induced immune responses that compared well with anti-spike IgG and microneutralization in a Covid-19 population with clinically significant illness.
This is the first study to report immunogenicity of a recombinant spike vaccine in humans. Overall the vaccine appears to be sufficient for further study.
otein nanoparticle vaccine. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2026920 (2020).
