Fig 1.
Simplified study schematic.
Table 1.
Participant demographics, infection and vaccine history in the saRNA (COVAC1) and non-saRNA participants by infection status.
Fig 2.
Anti-spike versus anti-nucleocapsid IgG.
2a. Baseline (pre-vaccination) anti-S and anti-N IgG in COVID-19 experienced (blue, n = 37) and COVID naïve (red, n = 38) participants as measured by ELISA. 2b. Anti-S and anti-N IgG two weeks following the 2nd UK authorised vaccine dose in COVID-19 experienced (n = 36) and naïve (n = 33). LOD; level of detection.
Fig 3.
Binding and neutralising antibody responses.
3a. Antibodies against SARS-CoV-2 Wuhan-hu-1 spike protein as measured by ELISA at baseline and two weeks following dose 1 and 2 of saRNA and mRNA vaccines in saRNA (COVAC1) participants (red and blue) and at baseline and two weeks following dose 1 and 2 of mRNA vaccines in non-saRNA participants (orange and green). 3b. Neutralising antibodies against SARS-CoV-2 Wuhan-hu-1 measured using pseudovirus at baseline and two weeks following the 2nd dose of saRNA and mRNA vaccines in saRNA participants (red and blue) and two weeks following the 2nd dose of mRNA vaccine in non-saRNA participants (orange and green). 3c. Neutralising antibodies against SARS-CoV-2 Wuhan-hu-1, Delta and Omicron BA.1 and BA.4/5 using pseudovirus two weeks following the second mRNA vaccine dose and the differences between groups. 3d. Fold decrease in neutralisation against Delta and Omicron BA.1 and BA.4/5 compared to Wuhan-hu-1 (y axis inverted) 3e. Correlation between binding antibodies against SARS-CoV-2 Wuhan-hu-1 spike protein (ELISA) and neutralisation (pseudovirus) against Wuhan-hu-1, Delta and Omicron BA.1 and BA.4/5 two weeks following the second mRNA vaccine dose. Number of samples included in the analysis indicated on graphs. Geometric mean titres (GMT) and standard deviation (sd) are shown. Differences between groups determined by Kruskall-Wallis and tested using Mann-Whitney. Median fold decrease within groups by Wilcoxon matched pairs signed rank test. Correlations by Spearman’s rank correlation coefficient. -, no exposure; +, single exposure; ++, two exposures; LOD, level of detection; WT, wildtype; Δ, Delta. Significant values displayed: **** p<0.0001; *** p<0.001; ** p<0.01; * p<0.05; ns, non-significant.
Fig 4.
4a. IFN-γ spot forming units (SFU) per million cells (ELISpot) from PBMC stimulated with SARS-CoV-2 spike peptide pools. 4b. Representative flow cytometry plots of SARS-CoV-2 specific CD4+ cells (CD40L+OX40+) in a vaccinated subject. 4c. Percentage of SARS-CoV-2 spike specific AIM+ non-naïve CD4+ cells (CD40L+OX40+) at baseline and two weeks following the second licensed vaccine dose in non-saRNA participants (orange and green) and two weeks following the second saRNA and mRNA vaccine doses in saRNA (COVAC1) participants (red and blue) 4d. Representative flow cytometry plots of SARS-CoV-2 specific CD8+ cells (CD69+CD137+) in a vaccinated subject. 4e. Percentage of SARS-CoV-2 spike specific AIM+ non-naïve CD8+ cells (CD69+CD137+) at baseline and two weeks following the second mRNA vaccine dose in non-saRNA participants (orange and green) and two weeks following the second saRNA and mRNA vaccine doses in saRNA participants (red and blue). 4f. Antigen specific CD8+:CD4+ ratio (geometric mean shown). 4g. Correlation between IFN-γ ELISpot and % antigen specific CD4+ and CD8+ T cells. Graphs are all on a logarithmic scale. Differences between groups determined using Kruskall-Wallis followed by Mann-Whitney for individual comparisons (displayed); Correlation by Spearman’s rank correlation coefficient; -, no exposure; +, single exposure; ++, two exposures; Significant values displayed: *** p<0.005 ** <0.01 *<0.05.
Table 2.
Summary table of experimental results (Geometric means).