SARS-CoV-2 virus lacking the envelope and membrane open-reading frames as a vaccine platform

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• The need for broadly protective vaccines against SARS-CoV-2 remains critical.
• Existing vaccines face challenges with emerging variants and duration of immunity.

Purpose of the Study:

• To develop and evaluate an attenuated SARS-CoV-2 vaccine candidate virus (ΔEM).
• To assess the immunogenicity and protective efficacy of the ΔEM vaccine in a hamster model.

Main Methods:

• Development of a replication-conditional SARS-CoV-2 vaccine virus (ΔEM) lacking envelope (E) and membrane (M) protein genes.
• Assessment of CD8 T-cell responses post-vaccination.
• Evaluation of protection against SARS-CoV-2 variants (Delta and Omicron XBB) in hamsters after primary and booster vaccination regimens.

Main Results:

• The ΔEM vaccine virus replicates only in cells expressing E and M proteins, ensuring safety in wild-type hosts.
• Vaccination with ΔEM induced CD8 T-cell responses against spike and nucleocapsid proteins.
• Two ΔEM vaccinations offered superior protection in lower respiratory tissues compared to a single dose against Delta and XBB variants.
• ΔEM as a booster enhanced protection in respiratory tissues compared to an mRNA vaccine booster.

Conclusions:

• The SARS-CoV-2 ΔEM vaccine candidate represents a feasible and potentially effective vaccine platform.
• The ΔEM vaccine demonstrates potential for broad protection and improved efficacy as a booster strategy.