VSV-ΔG-Spike Candidate Vaccine Induces Protective Immunity and Protects K18-hACE2 Mice against SARS-CoV-2 Variants

Area of Science:

• Virology and Immunology
• Vaccine Development
• Neuroscience

Background:

• Emergence of SARS-CoV-2 variants raises concerns about vaccine efficacy.
• Need to assess vaccine-induced immunity against diverse viral strains.
• Understanding variant-specific disease mechanisms, particularly neuroinflammation.

Purpose of the Study:

• To evaluate the protective efficacy of VSV-ΔG-spike vaccination against SARS-CoV-2 variants.
• To analyze the immune response and disease outcomes in a mouse model.
• To compare the brain's transcriptomic response to different variants and the effect of vaccination.

Main Methods:

• Utilized the K18-hACE2 mouse model for SARS-CoV-2 variant infection.
• Administered VSV-ΔG-spike vaccination prior to challenge.
• Assessed viral load, morbidity, mortality, brain immune response, and performed transcriptomic profiling.

Main Results:

• VSV-ΔG-spike vaccination conferred protection against alpha, beta, gamma, and delta SARS-CoV-2 variants.
• Vaccination led to reduced viral load in organs, prevented mortality, and mitigated severe brain immune responses.
• Comprehensive transcriptomic analysis revealed vaccination's ability to prevent variant-induced brain disease manifestations.

Conclusions:

• VSV-ΔG-spike vaccination demonstrates robust protection against a range of SARS-CoV-2 variants.
• The vaccine elicits a consistent immune response, irrespective of variant.
• Highlights the vaccine's potential for broad protection against current and future SARS-CoV-2 variants.