Abstract
The 2019 novel coronavirus, SARS-CoV-2, first reported in December 2019, has infected over 102 million people around the world as of February 2021 and thus calls for rapid development of safe and effective interventions, namely vaccines. In our study, we evaluated a DNA vaccine against SARS-CoV-2 in the Syrian hamster model. Hamsters were vaccinated with a DNA-plasmid encoding the SARS-CoV-2 full length spike open reading frame (ORF) to induce host cells to produce spike protein and protective immune responses before exposure to infectious virus. We tested this vaccine candidate by both intranasal (IN) and intramuscular (IM) routes of administration and complexing with and without an in vivo delivery reagent. Hamsters receiving prime-boost-boost IM-only vaccinations recovered body weight quicker, had decreased lung viral loads, and increased SARS-CoV-2-specific antibody titers compared to control vaccinated animals but, surprisingly, lung pathology was as severe as sham vaccinated controls. The IM/IN combination group showed no efficacy in reducing lung virus titers or pathology. With increasing public health need for rapid and effective interventions, our data demonstrate that in some vaccine contexts, significant antibody responses and decreased viral loads may not be sufficient to prevent lung pathology.
Highlights
Published: 12 May 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in December 2019, emerged as a highly transmissible and rapidly spreading disease
The disease it causes, coronavirus disease 2019 (COVID-19), in general can be characterized by symptoms of pneumonia including fever, cough, and fatigue and may induce cytokine storm syndrome which causes severe respiratory failure or distress and this is considered the main cause of death in patients with COVID-19 [1]
The spike protein covers the surface of the virus and binds to human host cell receptor angiotensin-converting enzyme 2 (ACE-2) to mediate viral cell entry [4], making it key to infection and a good target for neutralizing antibodies and protective immunity [5]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in December 2019, emerged as a highly transmissible and rapidly spreading disease. It was defined as a pandemic by the World Health Organization (WHO) within 4 months of its appearance [1] and has infected over 102 million people around the world as of February. Like SARS-CoV-1, SARS-CoV-2 vaccine approaches have focused on utilizing the viral spike protein to elicit protective immune responses [1,3]. The spike protein covers the surface of the virus and binds to human host cell receptor angiotensin-converting enzyme 2 (ACE-2) to mediate viral cell entry [4], making it key to infection and a good target for neutralizing antibodies and protective immunity [5]. Only one DNA vaccine, INO-4800 by Inovio/
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