Safety, tolerability, and immunogenicity of PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine in healthy adults: an open-label randomized phase I clinical trial.

Purpose: This phase I study aimed to assess the safety, tolerability, and immunogenicity of the PIKA-adjuvanted recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein subunit vaccine in healthy adults aged 18 years and older.

Materials and methods: This is a phase I, open-label, dose-escalation study at three dose levels (5 µg, 10 µg, and 20 µg) of the PIKA coronavirus disease 2019 (COVID-19) vaccine administered intramuscularly. The three vaccine arms are (A) subjects who have never received any COVID-19 vaccination or have had COVID-19 infection for >6 months prior to enrolment; (B1) subjects whose COVID-19 primary vaccination series was completed with an inactivated COVID-19 vaccine; and (B2) subjects whose primary series was completed with messenger RNA COVID-19 vaccine.

Results: Subjects who reported solicited adverse events (AEs) within seven days post-vaccination ranged from 35% to 60% within each vaccine arm. Most solicited AEs were mild local pain and tenderness. Systemic solicited AEs were only reported in Arm A. In all three vaccine arms, neutralizing antibody geometric mean titers were highest at day 28 (Arms B1 and B2) or day 35 (Arm A) than at baseline for all dose levels against the Wuhan (wild original SARS-CoV-2 virus, Wuhan-Hu-1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. These were sustained at day 183. Seroconversion rates at day 35 (Arm A, 85.7%-92.9%) or day 183 (Arms B1, 90.9%-100.0%, and B2, 18.2%-36.4%) and geometric mean fold rises were highest in the 5-µg dose level against all three variants.

Conclusion: The PIKA-adjuvanted recombinant SARS-CoV-2 S protein subunit vaccine showed promising immunogenicity profile with no safety concerns. A dose-dependent immune response was observed, with slight advantages seen in low-dose (5 µg and 10 µg) groups (ClinicalTrials.gov registration number: NCT05305300).