Figure 5.
Immunogenicity and protection efficacy of Delta-Omicron chimeric RBD-dimer vaccine
Groups of 6- to 8-week-old female BALB/c mice (n = 10) were immunized with two doses of 2-μg prototype or Delta-Omicron chimeric RBD-dimer using AddaVax as adjuvant, 21 days apart. PBS plus adjuvant was given as the sham control. Sera collected at 14 days post the second immunization for antibody titration.
(A) Mice sera were tested for neutralization of a panel of pseudotyped viruses displaying prototype, Alpha, Beta, Delta, Omicron (BA.1), and Omicron (BA.2) spike. The values are the GMT ± 95% confidence interval (CI). The horizontal dashed line indicates the lower limit of detection (LLOD).
(B) Radar plot demonstrating the neutralization profile of sera elicited by prototype vaccine or Delta-Omicron chimeric vaccine against five SARS-CoV-2 pseudotyped viruses.
(C–J) Random selection of five mice in each group were challenged with 6 × 105 TCID50 of Delta SARS-CoV-2 variant (CCPM-B-V-049-2105-8) (C–F) and the other five were challenged with 6 × 105 TCID50 of Omicron (BA.1) variant (CCPM-B-V-049-2112-18) at 58 days post the second immunization (G–J). Mice challenged with Delta variant had received Ad5-hACE2 intranasally 5 days before.
(C) Pulmonary Delta viral gRNA levels were detected by qRT-PCR.
(D) Pulmonary Delta viral sgRNA levels were detected by qRT-PCR.
(E) Plots show correlations and corresponding two-sided p values between pVNT50 of Delta variant and Delta viral gRNA.
(F) Analyses of pathological scores for lung tissues of mice challenged with Delta variant.
(G) Pulmonary Omicron viral gRNA levels were detected by qRT-PCR.
(H) Pulmonary Omicron viral sgRNA levels were detected by qRT-PCR.
(I) Plots show correlations and corresponding two-sided p values between pVNT50 of Omicron variant and Omicron viral gRNA.
(J) Analyses of pathological scores for lung tissues of mice challenged with Omicron variant.
For (C, D, G, and H), shown are the box and whiskers plots of 25th–75th percentile with median as center and whiskers of minimum to maximum percentile. p values were analyzed with two-tailed unpaired t test (ns, p > 0.05; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗∗p < 0.0001). For (E and I), red and gray lines indicate linear regression line and 95% CI, respectively. r and p values represent Spearman’s correlation coefficients and corresponding two-sided p values, respectively. Symbols represent individual mouse and may overlap for equal values. Horizontal dashed lines indicated the LLOD. For (F and J), the values are means ± SEM. p values were analyzed with two-tailed Mann-Whitney test (ns, p > 0.05; ∗∗p < 0.01; ∗∗∗∗p < 0.0001).