OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Figures

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  Figure 1. (A) Schematic representation of OVX033 vaccine candidate. OVX033 is a recombinant multimeric protein composed by the full-length Nucleocapsid (N) of the SARS-CoV-2 virus (Wuhan original strain), genetically fused to the self-assembling sequence OVX313 (oligoDOM®). (B) Study design: Hamsters were immunized twice 28 days apart with OVX033, OVX033 adjuvanted with SQ (OVX033+SQ), or saline. The animals were challenged by intranasal instillation of 104 TCID50 of one of the three SARS-CoV-2 strains, B.1 Europe (UCN19), Delta (B.1.617.2), or Omicron (B.1.1.529). After challenge, the animals were monitored daily for body weight up to 7 days and euthanized at either 4 or 7 days post-inoculation to measure viral loads in lungs and for lung histopathological analyses.

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  Figure 2. Immunization with OVX033 alone or adjuvanted with SQ protected against severe disease after challenge with SARS-CoV-2 B.1 Europe in a hamster model. Syrian Hamsters were immunized twice with OVX033, OVX033+SQ or saline, then challenged intranasally with 104 TCID50 of SARS-CoV-2 B.1 Europe (UCN19). (A) Percent weight change (mean ± SD), significance was measured at each time point. (B) Viral infection in lungs 4 days P.I., evaluated by TCID50 assay (left panel), RT-qPCR (middle panel) and in-situ hybridization (right panel) characterized by the percentage of area positively stained against viral RNA in lung sections. Individual values and mean ± 95% CI. (C) Lung histopathological analysis 7 days P.I. Left panel: heatmap showing severity for each lung histopathology parameter and animal (from 1 to 5). Airway inflammation/necrosis, peri-airway cuffing, peri-vascular cuffing, alveolar inflammation/necrosis. Scoring criteria are detailed in Supplementary Table S1 . Right panel: percentage of area with pneumonia as determined by image analysis of lung sections treated with hematoxylin and eosin (individual values and mean ± 95% CI). Significance was measured by Kruskal Wallis test,…

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  Figure 3. Immunization with OVX033 alone or adjuvanted with SQ protected hamsters against severe disease after challenge with SARS-CoV-2 VoC Delta (B.1.617.2) or Omicron (B.1.1.529), and induced N-specific humoral and cross-reactive cellular responses. (A) Lung viral load assessed by RT-qPCR 4 days post-challenge with Delta (left panel) or Omicron (right panel). (B) Mean percentage of area with pneumonia in the lung 7 days post-challenge with Delta (left panel) or Omicron (right panel) as determined by image analysis. Individual values and mean ± 95% CI. (C, D) Immunogenicity of OVX033 and OVX033+SQ in hamsters, 14 days after the second immunization. (C) N-specific seric IgG titers. Individual titers and GMT ± 95% CI. Significance was measured by Mann & Whitney tests on log-transformed data. (D) T-cell responses evaluated in spleen and lungs by IFNγ ELISpot. Histograms represents the mean ± SD number of IFNγ spot forming units (SFUs) among splenocytes or cells isolated from lungs, after overnight restimulation with N peptide pools from Wuhan, Delta or Omicron (15-mers overlapping by 11 amino acids). Significance was measured by Kruskal–Wallis test, followed by Mann & Whitney tests between…