A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells

• New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines. 

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

DNA vaccine

in vivo electroporation

preclinical development

SARS-CoV-2

universal SARS vaccine

angiotensin converting enzyme 2

membrane protein

neutralizing antibody

nucleoprotein

SARS-CoV-2 vaccine

virus spike protein

animal cell

animal experiment

animal model

animal tissue

Article

controlled study

coronavirus disease 2019

cross reaction

electroporation

female

histopathology

immunity

in vitro study

in vivo study

Leporidae

mouse

New Zealand White (rabbit)

nonhuman

preclinical study

receptor binding

SARS coronavirus

SARS-CoV-2 Alpha

SARS-CoV-2 Beta

SARS-CoV-2 Delta

SARS-CoV-2 Omicron

T lymphocyte

Publication and Content Type

ref (subject category)

art (subject category)