NVX-CoV2373, Novavax’s recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine containing a Matrix-M1 adjuvant, demonstrated safety and immunogenicity in phase 1 results of a phase 1/2 trial published in The New England Journal of Medicine.
Healthy adults aged 18 to 59 years received doses of either rSARS-CoV-2 with Matrix-M1, rSARS-CoV-2 alone, or placebo on days 0 and 21 and were followed through day 35. The trial’s primary outcome was to evaluate the safety and immunogenicity of 5-µg and 25-µg doses of rSARS-CoV-2 with or without a Matrix-M1 (50-µg) adjuvant.
Primary safety outcomes were reactogenicity and changes in laboratory values. The primary immunogenicity outcome was the anti-spike immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) unit response to rSARS-CoV-2 antigens, which contain the wild-type SARS-CoV-2 spike glycoprotein. Investigators also measured neutralizing antibodies and antigen-specific CD4+ T-cells.
Investigators randomized 131 patients into 5 groups: group A (n=23) received placebo, group B (n=25) received 25-µg doses of rSARS-CoV-2, group C (n=29) received 5-µg doses of rSARS-CoV-2 plus Matrix-M1, group D (n=28) received 25-µg doses of rSARS-CoV-2 plus Matrix-M1, and group E (n=26) received a single 25-µg dose of rSARS-CoV-2 plus Matrix-M1 followed by a single dose of placebo.
Local and systemic reactogenicity were either absent or mild in the majority of patients after each vaccination, with joint pain and fatigue the most common severe systemic events reported. The mean duration of reactogenicity events was 2 days or less for both vaccination periods. Abnormal laboratory values occurred in 10% (n=13) of participants, though they were transient, not associated with clinical manifestations, and did not worsen with repeat vaccinations.
At day 0 of the trial, anti-spike IgG geometric mean ELISA units (GMEUs) ranged from 105 to 116. By day 21, adjuvanted groups C, D, and E showed responses of 1984, 2626, and 3317 GMEUs, respectively, and their geometric mean fold rises (GMFRs) were higher than the groups without adjuvant by a factor of at least 10.
By day 35, groups with a second adjuvanted vaccination (groups C and D) had GMFRs about 100 times those who received rSARS-CoV-2 alone. GMEU levels in groups who received 2 adjuvanted vaccinations were similar to those seen in the convalescent serum of hospitalized coronavirus disease 2019 (COVID-19) patients (N=53,391).
GMEU responses of similar magnitude were seen with neutralizing antibodies after first and second doses of the adjuvanted vaccine. There was a strong correlation at day 35 between neutralizing antibody titers and anti-spike IgG GMEUs with the adjuvanted vaccine (correlation, 0.95; 95% CI, 0.92-0.96) not seen with the unadjuvanted vaccine. Additionally, adjuvanted regimens produced T-cell responses with a strong bias toward Th1 cytokines.
Responses to the 2-dose 5-µg and 25-µg adjuvanted vaccines were similar, highlighting the adjuvant’s dose-sparing effect.
Trial limitations included its small size, limited ethnic diversity, and the short follow-up period.
“The value of the second dose on day 21 for the 2-dose rSARS-CoV-2 plus Matrix-M1 regimen clearly demonstrated and warrants the use of this vaccine schedule,” investigators wrote.
Investigators also concluded that the Matrix-M1 adjuvant makes NVX-CoV2373 a competitive vaccine candidate by inducing high neutralizing antibody titers and T-cells with a predominant Th1 phenotype, addressing theoretical concerns of vaccine-enhanced COVID-19.
Disclosure: This clinical trial was supported by Novavax. Please see the original reference for a full list of authors’ disclosures.
Keech C, Albert G, Cho I, et.al. Phase 1-2 trial of SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. Published online September 2, 2020. doi:10.1056/NEJMoa2026920