Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

Abstract

A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

Fig. 1. Evaluation of nCoV-S(JET) DNA vaccine in Syrian hamsters.

a Experimental design. Groups of 8 hamsters each were vaccinated (vacc) with the nCoV-S(JET) DNA vaccine, PBS, or a MERS-CoV DNA vaccine and then challenged with 100,000 PFU of SARS-CoV-2 virus by the intranasal route. b PRNT50 and PsVNA50 titers from serum collected at indicated timepoints after 1 (open symbols) and 2 (closed symbols) vaccinations (assay limit = 20, gray shade). Bars represent GMT ± SD. c Average animal weights relative to starting weight. Symbols represent mean ± SEM. Viral RNA in d pharyngeal swabs and e lung homogenates (assay limit = 50 copies, gray shade). Bars GMT ± SD. f Infectious virus as measured by plaque assay (assay limit = 50 PFU, gray shade). Bars GMT ± SD. Bright field imagery of H&E staining of lung sections from g nCoV-S(JET) DNA, h PBS, or i MERS-CoV vaccinated hamsters where purple indicates areas of consolidation. ISH to detect SARS-CoV-2 genomic RNA in lung sections of j nCoV-S(JET) DNA, k PBS, and l MERS-CoV vaccinated hamsters. Rare, positive labeling in nCoV-S(JET) DNA vaccinated hamster lung sections were detected (arrows). Asterisks indicate that results were statistically significant, as follows: *p < 0.05; **p < 0.01; ***p < 0.001; ns not significant. Scale bars = 400 microns. Hamster drawing was provided by Jake Hooper (hjake@vt.edu), with permission.

Fig. 2. Evaluation of nCoV-S(JET) DNA vaccine in immunosuppressed Syrian hamsters.

a Experimental design. Groups of 8 hamsters each were vaccinated (vacc) with the nCoV-S(JET) DNA vaccine or PBS, immunosuppressed with cyclophosphamide (dashed vertical lines in d and e), and then challenged with 1,000 PFU of SARS-CoV-2 virus by the intranasal route. b PRNT50 and PsVNA50 titers from serum collected at indicated timepoints after 1 (open symbols) and 2 (closed symbols) vaccinations (assay limit = 20, gray shade). Bars represent GMT ± SD. c Lymphopenia was confirmed by hematology. d Average animal weights relative to starting weight. Symbols represent mean ± SEM. Viral RNA in e) pharyngeal swabs and f lung homogenates (assay limit = 50 copies, gray shade). Bars represent GMT ± SD. g Infectious virus as measured by plaque assay (assay limit = 50 PFU, gray shade). Bars represent GMT ± SD. A single animal from the PBS group succumbed on Day 9 post-exposure (open symbol in f and g). Bright field imagery of H&E staining of lung sections from h nCoV-S(JET) DNA or i PBS vaccinated hamsters where purple indicates areas of consolidation. ISH to detect SARS-CoV-2 genomic RNA in lung sections of j nCoV-S(JET) DNA and k PBS vaccinated hamsters. Rare, positive labeling in nCoV-S(JET) DNA vaccinated hamster lung sections were detected (arrows). Asterisks indicate that results were statistically significant, as follows: *p < 0.05; **p < 0.01; ***p < 0.001; ns not significant. Scale bars = 400 microns. Hamster drawing was provided by Jake Hooper (hjake@vt.edu), with permission.