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. 2023 Jun 19:14:1188605.
doi: 10.3389/fimmu.2023.1188605. eCollection 2023.

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

Charlotte Primard  1 , Elodie Monchâtre-Leroy  2 , Judith Del Campo  1 , Séverine Valsesia  1 , Elsa Nikly  1 , Marion Chevandier  1 , Franck Boué  2 , Alexandre Servat  2 , Marine Wasniewski  2 , Evelyne Picard-Meyer  2 , Thomas Courant  3 , Nicolas Collin  3 , Francisco J Salguero  4 , Alexandre Le Vert  1 , Delphine Guyon-Gellin  1 , Florence Nicolas  1
Affiliations

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

Charlotte Primard et al. Front Immunol. .

Abstract

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) protein of SARS-CoV-2 genetically fused to oligoDOM®, a self-assembling domain which improves antigen immunogenicity. OVX033 including N as an antigenic target is proposed as new vaccine candidate providing broad-spectrum protection against sarbecoviruses. OVX033 demonstrated its ability to trigger cross-reactive T cell responses and cross-protection against three variants of SARS-CoV-2 (B.1 Europe, Delta B.1.617.2, and Omicron B.1.1.529) in a hamster challenge model, as evidenced by lower weight loss, lower lung viral loads, and reduced lung histopathological lesions.

Keywords: T cell immunity; broad-spectrum protection; cross-reactive immune responses; lung histopathology; lung viral load; recombinant nucleocapsid; sarbecovirus vaccine; universal vaccine.

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Conflict of interest statement

Author TC is an employee of VFI. Author NC is co-founder and an employee of VFI. CP, JC, SV, EN, AV, DG-G, and FN are employees of Osivax. MC was employee of Osivax at the time of her participation in the study, and her current affiliation is Manpower France in Sanofi Marcy L’Etoile, France. AV, DG-G. and FN are shareholders and executive members of Osivax. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
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.
Figure 2
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, followed by Mann & Whitney tests between treated groups and mock-immunized group. *p < 0.05 and **p < 0.01.
Figure 3
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 treated groups and mock-immunized group. *p < 0.05 and **p < 0.01.
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