RESUMO
Background: NVX-CoV2373, an adjuvanted, recombinant SARS-CoV-2 spike (rS) protein vaccine, consistently demonstrated protective efficacy against COVID-19 in clinical trials and has received regulatory authorizations or approvals worldwide. Methods: PREVENT-19 (NCT04611802) is a phase 3, randomized, observer-blinded, placebo-controlled trial evaluating safety, immunogenicity, and efficacy of NVX-CoV2373 in ≈30 000 participants ≥18 years in the United States and Mexico. Vaccine humoral immune response (ie, serum immunoglobulin [IgG] antibodies, hACE2 receptor binding inhibition antibodies, and neutralizing antibodies to SARS-CoV-2) (ancestral strain) was assessed in 1200 participants randomly selected and equally divided between participants 18-64 and ≥65 years. Results: In the per protocol analysis, NVX-CoV2373 induced vigorous serum antibody responses among the 1063 analyzed participants who were SARS-CoV-2 seronegative at baseline, received both doses of study treatment, and had serology results available 2 weeks after dose 2. Geometric mean (GM) responses in both younger and older adults were higher among recipients of vaccine versus placebo for IgG (64 259 vs 121 and 37 750 vs 133 ELISA units, respectively), hACE2 receptor binding inhibition GM titers (GMTs) (222 vs 5 and 136 vs 5, respectively), and neutralizing antibody GMTs (1303 vs 11 and 900 vs 11, respectively). Humoral responses were 30-40% lower in participants ≥65 years or HIV-positive; however, seroconversion rates were high and comparable between the age cohorts, regardless of HIV serostatus. Conclusions: NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy.
RESUMO
BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).