Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico

Abstract

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.

Figure 1.

Distribution of participants by treatment groups and age cohorts. Abbreviations: FAS, full analysis set; GCP, good clinical practices; ITT, intent-to-treat; NP, nucleoprotein; PCR, Polymerase Chain Reaction; PP-IMM, Per-Protocol Immunogenicity analysis set; PP-IMM-2, Per-Protocol Immunogenicity analysis set 2.

Figure 2.

SARS-CoV-2 neutralizing antibody responses in participants who were seronegative/RT-PCR-negative at baseline. Panel A: participants 18–64 years, Panel B: participants ≥65 years. Abbreviations: MN, microneutralization; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

SARS-CoV-2 anti-Spike IgG antibody responses in participants who were baseline seronegative/RT-PCR-negative at baseline participants. Panel A: participants 18– to 64 years, Panel B: participants ≥ 65 years. Abbreviations: ELISA, enzyme-linked immunosorbent assay; EU/mL, ELISA units per mL; IgG, immunoglobulin; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 4.

hACE2 receptor inhibition antibody responses in participants who were baseline seronegative/RT-PCR-negative at baseline participants. Panel A: participants 18 to 64 years, Panel B: participants ≥ 65 years. Abbreviations: hACE2, human angiotensin converting enzyme 2; RT-PCR, reverse transcriptase polymerase chain reaction.