An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters

Citation

Authors: Leventhal SS. et al.
Year: 2021
Journal: Microorganisms 9 1040
Applications: in vivo / DNA / in vivo-jetPEI

Method

- Saline vaccinations were prepared by diluting 100 µg of plasmid DNA in sterile DPBS solution. - Complexed vaccinations were prepared by complexing 25 µg of DNA to in vivojetPEI (Polyplus Transfection, New York, NY, USA) following recommended protocol, scaled up to make a stock for all complexed vaccinations. Briefly, DNA plasmid and in vivo-jetPEI were diluted in provided 10% glucose solution before mixing and incubation with reagent. - Hamsters received either Sp_pVax1 via IM injections with 100 µg of DNA diluted in saline (Sp-Saline IM), IM with 50 µg of DNA complexed to in vivo delivery reagent (Sp-complex IM), or IN with 50 µg of DNA complexed to in vivo delivery reagent (Sp-complex IN). - An identical boost vaccination was given 3 weeks post-prime, and hamsters were challenged IN three weeks post-boost with 1000 TCID50 of SARS-CoV-2 (ID50 = 5 TCID50 [15]). In our study, while neither the saline or PEI-complexed DNA vaccinated animals significantly decreased viral shedding or viral loads, there was a trending decrease in all three vaccination groups compared to controls. Consistent with the similar viral loads across control and spike vaccinated groups, our ELISA and neutralization assay data suggested that our prime-boost vaccine regimen was poorly immunogenic, even when the vaccine was complexed to PEI.

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.

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