The safety, reactogenicity, and immunogenicity of the self-amplifying mRNA COVID-19 vaccine GRT-R910 as a booster in healthy adults.

BACKGROUND: GRT-R910 (Gritstone bio, Inc), a self-amplifying mRNA vaccine expressing SARS CoV-2 (D614G) spike protein and T-cell epitopes, was evaluated as a booster vaccine in a phase 1 study in 2021-2022. METHODS: This open-label, dose escalation study enrolled healthy adults ≥112 days after completion of primary COVID-19 vaccination, booster of approved mRNA COVID-19 vaccine, or known SARS-CoV-2 infection. Persons aged 18-60 years received single doses of 3 or 6 μg GRT-R910 (n = 10/group). Persons >60 years of age received GRT-R910 at 3, 6, or 10 μg (n = 8-10/group). Safety and immunogenicity responses were assessed for 1 year after vaccination. RESULTS: We enrolled 48 participants. Most participants developed mild-to-moderate systemic reactions and/or injection site tenderness. Eight of 48 (17%) had severe systemic reactions. Pseudovirus neutralizing antibody geometric mean fold rise (GMFR) responses against SARS-CoV-2 (D614G) at Day 29 and Day 181, respectively, among those ≤60 years were 5.2 (95% CI 2.1, 13.3) and 6.1 (2.8, 13.2) after 3 μg, and 3.6 (1.3, 10.4) and 2.4 (0.2, 33.0) after 6 μg. The GMFR responses among those aged >60 years were 8.1 (2.1, 31.4) and 8.2 (1.2, 57.5) after 3 μg, 2.7 (1.1, 6.7) and 1.8 (0.5, 6.7) after 6 μg, 3.3 (1.5, 7.4) and 3.3 (1.3, 8.0) after 10 μg. The 6 μg dose group in those ≤60 years, 6 μg and 10 μg dose groups in those aged >60 years had higher baseline geometric mean titers (GMTs), which, in turn may have lowered the GMFR for those groups. GMFR persistence until Day 181 in most groups indicated these boosts were associated with durable increases in GMFR. Neutralizing antibody titers assessed via focus reduction neutralization test against SARS-CoV-2 D614G largely mirrored the PsVNA findings. CONCLUSIONS: GRT-R910 was safe but reactogenic when administered to previously vaccinated or infected adults and boosted anti-SARS-CoV-2 neutralizing antibody responses in most participants with responses that appeared durable for up to 6 months. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04776317. CLINICALTRIALS: gov ID NCT04776317.

Duke Scholars

Author David Charles Montefiori Surgery, Surgical Sciences