Safety and immune response kinetics of GRAd-COV2 vaccine: phase 1 clinical trial results

Abstract

Despite the successful deployment of efficacious vaccines and therapeutics, the development of novel vaccines for SARS-CoV-2 remains a major goal to increase vaccine doses availability and accessibility for lower income setting. We report here on the kinetics of Spike-specific humoral and T-cell response in young and old volunteers over 6 months follow-up after a single intramuscular administration of GRAd-COV2, a gorilla adenoviral vector-based vaccine candidate currently in phase-2 of clinical development. At all three tested vaccine dosages, Spike binding and neutralizing antibodies were induced and substantially maintained up to 3 months, to then contract at 6 months. Potent T-cell responses were readily induced and sustained throughout the study period, with only minor decline. No major differences in immune response to GRAd-COV2 vaccination were observed in the two age cohorts. In light of its favorable safety and immunogenicity, GRAd-COV2 is a valuable candidate for further clinical development and potential addition to the COVID-19 vaccine toolbox to help fighting SARS-CoV-2 pandemic.

Fig. 1. SARS-CoV-2 humoral, cellular and anti-vector response elicited by GRAd-COV2 vaccination over time.

SARS-CoV-2 humoral, cellular and anti-vector response induced by GRAd-COV2 vaccination and measured at the day of vaccination (w0) and 1, 2, 4, 8, 12 and 24 weeks (w1, w2, w4, w8, w12, w24 respectively) after vaccination over 6 months follow up. N = 15 for each study arm. a IgG binding to S1-S2 measured by CLIA. Data are expressed as arbitrary unit (AU)/ml. b SARS-CoV-2 specific IgG measured by ELISA on recombinant full-length spike protein. c SARS-CoV-2 specific IgG measured by ELISA on RBD. Data in both b and c are expressed as binding antibody units (BAU)/ml. d Neutralizing activity detected by SARS-CoV-2 microneutralization assay. e Neutralizing activity detected by Spike (D614G)-pseudotyped lentivirus neutralization assay. SARS-CoV-2 neutralization titers are expressed as MNA₉₀, or the reciprocal of serum dilution achieving 90% neutralization, or in International Units (IU)ml, in d and e respectively. f Spike-specific T cell response measured by IFNγ ELISpot on frozen PBMC. Data are expressed as IFNγ spot forming cells (SFC) per 10⁶ PBMC. g Neutralizing titers to the GRAd vector, measured by a neutralization assay based on SEAP reporter gene activity inhibition. Throughout, blue and red color shades identify younger (Y-circles) and older age (O-triangles) cohorts, respectively, and color tone increase with vaccine dose: low dose (LD, 5 × 10¹⁰ vp), intermediate dose (ID, 1 × 10¹¹ vp) and high dose (HD, 2 × 10¹¹ vp). Square symbols indicate human convalescent serum obtained from either previously hospitalized (hosp-dark gray) or from non-hospitalized (non-hosp-light gray) COVID-19 patients. NIBSC 20/130 research reagent plasma (red diamond) is shown for reference (panels b to c). Data are shown either as the group geometric mean and 95% confidence interval (CI) (panels a, b, c, f and g) or as individual points and box and whiskers indicating median and interquartile range, with whiskers ranging from min to max (panels d and e). Negative samples were assigned a value of ½ the LOD.

Fig. 2. Immune response before and after SARS-CoV-2 infection in a GRAd-COV2 vaccinated volunteer.

a Timeline detailing the SARS-CoV-2 infection case in terms of vaccination, in-study and out-of-study visits, symptoms onset and swabs outcome until resolution. b IgG binding to S1-S2 measured by CLIA in arm 3 (high dose vaccine in younger age volunteers), with IgG kinetics in the COVID-19 case depicted in red and all remaining volunteers in gray for context. Below each study visit indicated on x axis, the outcome of a qualitative CMIA detecting anti-nucleocapsid (N) IgG is reported for the COVID-19 case. c SARS-CoV-2 neutralizing activity time course in serum from the COVID-19 case, detected by MNA. d T cell response to Spike in arm 3 detected by IFNγ ELISpot on freshly isolated PBMC 2 weeks after vaccination, with the COVID-19 case depicted in red and all remaining volunteers in gray for context. The horizontal line is set at median. e Spike and N T-cell response time course in the COVID-19 case, detected by IFNγ ELISpot on frozen PBMC. DMSO, the peptide pools diluent, represents the assay negative control. The arrow in panels b, c and e highlight timing of SARS-CoV-2 infection. Postinfection visits data in panels c and e are depicted in red.