Immunogenicity and Protectivity of Sputnik V Vaccine in hACE2-Transgenic Mice against Homologous and Heterologous SARS-CoV-2 Lineages Including Far-Distanced Omicron BA.5

Abstract

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant.

Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5.

Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant.

Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus.

Keywords: COVID-19 vaccine; cross-protection; hACE2-transgenic mice; immunogenicity; vector vaccine.

Figure A1

Histopathological analysis of the lungs of K18-hACE2 mice 7 days after infection with SARS-CoV-2 (B.1.1.529 (Omicron) sublineage BA.5 or B.1.1.1 (Wuhan)) with Sputnik V vaccination (vaccine group) or without vaccination (placebo group). (A) Architecture of the perivascular space (left column) and peribronchiolar space (middle column), H&E, bar = 100 µm; architecture of a full mouse lung section (right column), H&E, bar = 2 mm. (B) 5-point assessment of perivascular inflammation; 5-point score for peribronchiolar inflammation; acute lung injury (ALI) score. The boxes show the interquartile range, the whiskers show the range from minimum to maximum, and the horizontal line shows the median value. Each point on the graph corresponds to 1 field of view/1 vessel/1 bronchiole, 10 points were measured for each mouse, the data are summarized for all animals of one experimental group. The red color of the boxes corresponds to the placebo group, the light blue color represents the vaccinated group. Significant differences between vaccinated Sputnik V and non-vaccinated mice were measured using the two-tailed Mann-Whitney test (**** p < 0.0001, * p < 0.0332).

Figure 1

(A) Study design. (B) RBD-specific IgG antibody levels in the blood sera of Sputnik V-vaccinated mice (n = 5) to SARS-CoV-2 variants B.1.1.1, B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.5. (C) Levels of NtAb in the blood sera of Sputnik V-vaccinated mice (n = 10) to the SARS-CoV-2 variants B.1.1.1, B1.1.7 (Alpha), B.1.351 (Beta), B.1.1.28/P.1 (Gamma), B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.2, BA.5. (D) The number of proliferating CD4+ T cells derived from spleens of Sputnik V- and PBS-vaccinated mice (n = 5 per group) in response to restimulation by recombinant glycoproteins of the B.1.1.1, B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.5. (E) The number of proliferating CD8+ T cells derived from spleens of Sputnik V- and PBS-vaccinated mice (n = 5 per group) in response to restimulation by recombinant glycoproteins of the B.1.1.1, B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.5. (F) Concentration of IFN-γ in the medium from splenocytes restimulated with glycoproteins of the B.1.1.1, B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.5. (G) Concentration of IL-2 in the medium from splenocytes restimulated with glycoproteins of the B.1.1.1, B.1.617.2 (Delta) and B.1.1.529 (Omicron) sublineages BA.1, BA.5. Dots represent individual data points. In B-C horizontal lines represent geometric mean titers (values are indicated above each group), and whiskers are 95% CIs. In D-G horizontal lines represent mean (values are indicated above each group), and whiskers are SD. Groups were compared by non-parametric ANOVA (Friedman’s test) with Dunn’s multiple comparison post-test (ns—not significant, * p < 0.05, ** p < 0.01).

Figure 2

Experiment scheme. K18-hACE2-transgenic mice were immunized twice with vaccine or placebo (PBS buffer). At day 7 after second vaccine/placebo dose mice were challenged with SARS-CoV-2 virus.

Figure 3

(A) Macrophotographs and slide scans of the lungs of unvaccinated (bottom row) and vaccinated with Sputnik V (top row) K18-hACE2 mice challenged with SARS-CoV-2; hematoxylin and eosin (H&E) staining; bar = 2 mm. (B) Histopathological analysis of K18-hACE2 mouse lungs: perivascular space (left column) and peribronchiolar space (right column) of mouse lungs; H&E; bar = 100 µm. (C) Acute lung injury (ALI) score; 5-point score for peribronchiolar inflammation; 5-point assessment of perivascular inflammation. The boxes show the interquartile range, the whiskers show the range from minimum to maximum, and the horizontal line shows the median value. Each point on the graph corresponds to 1 field of view/1 vessel/1 bronchiole, 10 points were measured for each mouse, the data are summarized for all animals of one experimental group. The red color of the boxes corresponds to the placebo group, the light blue color represents the vaccinated group, and the white color of the boxes to the group of intact mice. Significant differences between vaccinated Sputnik V and non-vaccinated mice were measured using the two-tailed Mann–Whitney test (**** p < 0.0001, ns—not significant).

Figure 4

(A) Viral load (lgTCID₅₀/_mL) in lungs of vaccinated with Sputnik V (Vaccine) and non-vaccinated (placebo) mice at day 4 after SARS-CoV-2 challenge (n = 4 per Wuhan-Delta groups, n = 5 per Omicron BA.5 group). Significant differences between vaccinated Sputnik V and non-vaccinated mice were measured using the two-tailed Mann-Whitney test (* p < 0.05). (B,D,F,H,J,L) Weight dynamics (mean ± SEM) in Vaccine and Control groups after challenge with SARS-CoV-2 variants B.1.1.1 (B), B.1.1.7 (D), B.1.351 (F), B.1.1.28/P.1 (H), B.1.617.2 (J), B.1.1.529 BA.5 (L) (n = 8/per group). Survival (%) in Vaccine and Control groups after challenge with SARS-CoV-2 variants B.1.1.1 (C), B.1.1.7 (E), B.1.351 (G), B.1.1.28/P.1 (I), B.1.617.2 (K), B.1.1.529 BA.5 (L,M) (n = 8/per group). Significant differences between vaccinated Sputnik V and non-vaccinated mice were measured using the Log-rank (Mantel–Cox) test (*** p <0.001, ** p < 0.01, * p < 0.05).