The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused close to 800 million infections and over 7 million deaths worldwide. In addition to its impact on human health, the virus has shown cross-species transmission, including spillover into mustelids such as mink. Here, we evaluated the safety, immunogenicity, and efficacy of a live attenuated Newcastle disease virus (NDV) vaccine expressing a prefusion-stabilized (PFS) SARS-CoV-2 spike protein (pS), delivered intranasally in domestic ferrets, included in the study as a well-established model of upper respiratory infection in humans, and a representative mustelid species. The vaccine (NDV-PFS) was safe and immunogenic, promoting a systemic antibody response and plasma neutralizing activity against the Ancestral, Delta, and, to a lesser degree, Omicron variant. Upon intranasal challenge with the Ancestral strain, vaccination conferred protection against virus replication, reducing SARS-CoV-2 RNA in the nasal turbinates by approximately five orders of magnitude, and eliminating detectable virus antigen in turbinates by immunohistochemistry. Importantly, both single- and double-dose regimens reduced SARS-CoV-2 replication to a similar extent, indicating that this vaccine platform may be amenable to single-dose administration. Overall, NDV-PFS proved to be a safe, immunogenic, and protective intranasal vaccine against SARS-CoV-2 in ferrets. As the first study to evaluate an NDV-vectored vaccine in this species, this study expands the range of animals in which this platform has proven effective, and supports further development of NDV-based mucosal vaccines for respiratory pathogens in multiple species.

Background Rhodococcus equi-specific hyperimmune plasma (Re-HIP) is routinely administered to neonatal foals to help prevent rhodococcal pneumonia. In addition to pathogen-specific immunoglobulins, frozen plasma products (FPPs) contain electrolytes that may exceed concentrations found in neonatal foal plasma. Because FPPs are also used to treat failure of passive transfer and sepsis, understanding their effects on neonate homeostasis is crucial. This study evaluated the effects of administration of Re-HIP on the serum concentrations of Na+, Cl-, K+, albumin, and globulin of healthy neonatal foals.Key Findings The concentration of Na+ was high in Re-HIP when compared with normal plasma values. Administration of Re-HIP resulted in an increase in serum Na+, Cl-, albumin, and globulin concentrations in neonatal foals.Significance The serum electrolyte changes seen after Re-HIP administration were likely of no clinical significance in healthy foals. However, the administration of hypernatremic plasma to septic or dehydrated foals could exacerbate electrolyte imbalances. These results suggest that caution and close monitoring are warranted when administering FPPs to critically ill foals.

Parrot bornavirus 4 (PaBV-4) remains poorly characterized with respect to the cellular determinants of its host range, genetic adaptation, and interactions with related orthobornaviruses. Here, we performed an in-depth in vitro characterization of PaBV-4 by evaluating its replication kinetics in avian and mammalian cell cultures, whole-genome sequencing during serial passage, and virus interference studies. Replication kinetics showed that PaBV-4 could establish persistent infection in most avian but no mammalian cell lines, with highest magnitude of propagation in quail fibrosarcoma (QT-35) and duck embryo (CCL-141) fibroblasts, although turkey embryo fibroblasts were not permissive. Sequencing of viral genomes from QT-35, CCL-141, and DF-1 (immortalized chicken fibroblasts) after ~ 24 passages showed only limited genetic diversification, with no evidence of host-specific molecular adaptation despite differences in cellular permissivity, indicating PaBV-4 genomic stability. QT-35, CCL-141, and DF-1 that were persistently infected with PaBV-4 or aquatic bird bornavirus-1 (ABBV-1; a related orthobornavirus) completely inhibited establishment of secondary infection with the other virus, whereas simultaneous coinfection favored PaBV-4 compared to ABBV-1 replication. In contrast, only transient inhibition of Newcastle disease virus (NDV; a distantly related mononegavirus) replication was observed in PaBV-4-persistently infected cells. Collectively, these findings demonstrate that cellular permissivity, rather than rapid viral adaptation, is the principal determinant of PaBV-4 replication in vitro and demonstrate strong viral interference among different orthobornavirus species.

Equine herpesvirus-1 (EHV-1) is ubiquitous in the horse population, but prevalence estimates have ranged from 3 to 88% depending on the population and method of sampling. No prevalence studies have been carried out in Ontario, Canada. The objective of this study was to measure the prevalence of EHV-1 shedding in healthy broodmares in Ontario. A total of 381 mares from 42 farms in Ontario were sampled, including pregnant and barren broodmares. Samples were collected from the nose, vagina, and blood of each mare up to 6 times from December 2016 through October 2017 using a cross-sectional study design. The EHV-1 glycoprotein B (gB) copy number was measured using droplet digital polymerase chain reaction (ddPCR). A survey was completed at time of sampling regarding signalment, pregnancy status, and vaccination. Overall, 85% of the mares sampled were positive for EHV-1 from at least one site, on at least one occasion. Samples were positive 8.1%, 15.8%, and 17.2% of the time from the nose, vagina, and white blood cells, respectively. Pregnant mares had increased odds of shedding virus from the nose [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.03 to 2.18, P = 0.037]. Vaccination only reduced the odds of virus presence in blood (OR = 0.70, 95% CI: 0.49 to 0.99, P = 0.043). Advanced gestation appeared to also have a sparing effect on virus presence in blood (OR = 0.89, 95% CI: 0.85 to 0.93, P < 0.001). Most mares in Ontario were positive for EHV-1 despite being healthy and vaccinated, although the amount of viral DNA detected was extremely low. In addition, the vagina was identified as a source of viral shedding.

Macrophage populations in the lung, including resident alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs), recognize the inhaled particulates in barn dust that cause severe equine asthma and orchestrate an immune response though the cytokines they produce. Despite their importance, the specific contributions of these macrophage subsets to lower airway inflammation remain poorly understood. This exploratory in vitro study investigated the likely contributions of AMs and MDMs from healthy horses to the early inflammatory response using RNA-seq. If biologically important contrasts were identified, future studies to elucidate differences in AM and MDM function in severely asthmatic horses could be undertaken. AMs and MDMs from six healthy female Standardbred horses were exposed for 6 h to a mixture of fungal spores, lipopolysaccharide, and silica microspheres (FLS), which represents the major components of barn dust, with serum-free cell culture medium as the control. Equine AMs and MDMs exposed to FLS showed broadly similar transcriptional responses, with cytokine signalling emerging as the dominant biological theme in both cell types. At an exploratory FDR threshold of 0.25, gene set enrichment analysis indicated that “JAK-STAT/IL-15 signalling pathway”, “NOD-like receptor signalling pathway”, and “infection/C-type lectin receptor” had greater enrichment in FLS-exposed MDMs than AMs. These exploratory data indicate that equine AMs and MDMs mount largely overlapping cytokine responses to the elements that contribute to exacerbation of severe equine asthma, but also exhibit cell-type specific pathway differences. This work establishes the baseline for future studies testing the hypothesis that in horses with severe equine asthma, AMs and MDMs each have altered function that contribute uniquely to disease pathogenesis.

Background: Due to the wide host range of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination has been recommended for susceptible species in zoological collections, particularly to protect endangered species. The Zoetis® Experimental Mink Coronavirus Vaccine (Subunit) was temporarily authorized in 2021–2024 for emergency use in North America for this purpose. However, there are limited data regarding its safety or efficacy in non-domestic mammals. The present study was conducted to assess the ability of this vaccine to elicit serum neutralizing titers against SARS-CoV-2 in selected animals from the Toronto Zoo (TZ) vaccinated during 2022. Methods: Serum samples were collected from 24 individuals across four families (Cervidae, Felidae, Ursidae, and Hyaenidae) and tested using a surrogate virus neutralization test (sVNT) and a plaque-reduction neutralization test (PRNT). Results: The results showed that all species developed some neutralizing titers after at least one vaccine dose, except for polar bears, which showed no seroconversion. Felids and hyenas had the highest neutralizing titers, which peaked at 3 and declined between 4 and 6 months after boost. These differences may stem from species-specific immune responses or lack of vaccination protocols tailored to individual species. Conclusions: While natural infection with SARS-CoV-2 could not be ruled out in the cohort of this study, insights from our results have the potential to inform future vaccine recommendations for non-domestic species. Furthermore, our study highlighted the value of competitive assays in assessing serological responses across a broad range of exotic species, for which reagents, such as anti-isotype antibodies, are often unavailable.

Aquatic bird bornavirus 1 (ABBV1), an orthobornavirus in the family Bornaviridae, displays a broad host range among avian species, including poultry. The pathogenesis of orthobornaviruses, at least in mammals and psittacines, appears to be mediated by the host immune response against the infected nervous tissue, with younger animals showing a milder disease due to immune tolerance. Here, we tested the ability of ABBV1 to infect domestic turkeys (Meleagris gallopavo), with a focus on evaluating the impact of age at infection. Cohorts of 6-week-old (old) and day-old (young) male turkeys were divided into virus-inoculated and control groups, and kept for up to 12 weeks. Results showed that turkeys of both ages were susceptible to ABBV1 infection by intramuscular administration, following a centripetal and limited centrifugal spread, although infection appeared delayed in old compared to young birds. Notably, only young turkeys developed clinical signs and more frequent inflammation of the central nervous system, indicating that infection at a very early age is unlikely to induce tolerance to ABBV1 infection.

Abstract Background It is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling. Results Microbiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage. Conclusion These findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Objective Our objective was to determine whether equine herpesviruses 1 (EHV-1) viral nucleic acids could be detected immediately after foaling from nasal and vaginal swabs, whole blood, and placental tissue of healthy mares. Animals, procedure, and results Nasal and vaginal swabs, EDTA blood, and placental tissue (296 samples) were collected from 74 clinically healthy postpartum broodmares within 24 h after giving birth to live, clinically healthy foals. All samples were tested (PCR) for nucleic acids of neuropathogenic and non-neuropathogenic strains of EHV-1, and all were negative. Conclusion and clinical relevance As EHV-1 was not detected in the immediate postpartum period in healthy mares with uncomplicated foaling, we inferred that EHV-1-positive samples from aborting mares and/or EHV-1 detection in fetal membranes indicate EHV-1-associated abortion.

Aquatic bird bornavirus 1, an orthobornavirus in the family Bornaviridae, displays a broad host range among avian species, including poultry. The pathogenesis of orthobornaviruses is mediated by the host immune response against the infected nervous tissue, with younger animals showing a milder disease due to immune tolerance. Here, we tested the ability of ABBV1 to infect domestic turkeys (Meleagris gallopavo), with a focus on evaluating the impact of age at infection. Cohorts of 6-week-old (old) and day-old (young) male turkeys were divided into virus-inoculated and control groups, and kept for up to 12 weeks. Results showed that turkeys of both ages were susceptible to ABBV1 infection by intramuscular administration, following a centripetal and limited centrifugal spread, although infection appeared delayed in old compared to young birds. Notably, only young turkeys developed clinical signs and more frequent inflammation of the central nervous system, indicating that infection at a very early age is unlikely to induce tolerance to ABBV1 infection.

Boar taint, an unfavorable odor in the meat of intact male pigs, is caused primarily by the accumulation of two compounds: androstenone and skatole. This multifactorial trait is regulated by numerous dietary, management and genetic factors. At the mechanistic level, there are many genes known to be involved in boar taint metabolism. Cytochrome P450 2E1 (CYP2E1) impacts boar taint through the phase I metabolism of skatole. The aim of this study was to identify single-nucleotide polymorphisms (SNPs) within the CYP2E1 gene promoter and explore their relationship with the expression of CYP2E1 mRNA and protein. Sequencing of the promoter region using pools of genomic DNA identified seven promoter region SNPs at −159, −586, −1693, −1806, −2322, −2369 and −2514 bp upstream of the ATG start site. Genomic DNA was obtained from 65 boars from the three major swine breeds: Duroc, Landrace and Yorkshire, and individual animals were genotyped for the identified SNPs. RNA was isolated from liver tissue and quantitative PCR was performed to measure CYP2E1 gene expression, while levels of CYP2E1 protein in liver were measured by Western blotting. Significant within-breed variation in CYP2E1 protein and mRNA expression was observed, indicating significant differences in gene expression among individuals. However, levels of CYP2E1 mRNA and protein were not significantly correlated. Two SNPs within the promoter were significantly associated with CYP2E1 mRNA expression, but not with protein expression. This study provides evidence of additional mutations affecting the gene expression of CYP2E1 and suggests that factors that affect the differences in translation of CYP2E1 mRNA may also be important in affecting skatole metabolism.

An 11-year-old, female, spayed, soft-coated Wheaten terrier presented for acute onset of neurological signs. On presentation, neurological examination showed right thoracic and pelvic limb proprioceptive deficits, absent right menace reflex, and weak right nasal septum response. A left thalamocortical lesion was localized. On thoracic auscultation, an arrhythmia was noted, and electrocardiography showed frequent ventricular premature complexes and rare runs of ventricular tachycardia. Echocardiography identified an interventricular septal mass extending into the lumen of the left ventricle. Thalamocortical metastasis secondary to the cardiac mass was suspected to be the cause of the patient's neurological signs. Humane euthanasia was elected by the owner due to the patients clinical status and poor prognosis. A postmortem examination diagnosed hemangiosarcoma of the interventricular septum, the right ventricular free wall, and left ventricular free wall. The left ventricle adjacent to the paraconal groove showed myocardial necrosis and inflammation. Metastases to the brain and secondary intracranial hemorrhage were found which were suspected to be the cause of the antemortem neurological signs. Concurrent pulmonary and hepatic metastases were noted. This report describes a rare presentation of an intracardiac hemangiosarcoma of the interventricular septum, right ventricle, and left ventricle in a patient presenting with neurological signs.

Equine enterotyphlocolitis is an inflammatory process of the intestinal tract of horses that is associated with multiple etiologic agents and risk factors. Most clinical cases do not have an etiologic diagnosis. We describe here the pathogens detected and the histologic lesions found in horses with enterotyphlocolitis in Ontario that were submitted for postmortem examination, 2007–2019. We reviewed the medical records of 208 horses that fulfilled inclusion criteria. Cultures were positive in 67 of 208 (32%) equids for Clostridium perfringens, in 16 of 208 (8%) for Clostridioides difficile, and in 14 of 208 (7%) for Salmonella spp.; 6 of 208 (3%) were positive for Neorickettsia risticii by PCR assay. One horse was positive in a Rhodococcus equi PCR assay. All horses tested by PCR assay for equine coronavirus and Lawsonia intracellularis were negative. The histologic lesions were characterized as follows: 6 of 208 (3%) enteritis, 5 of 208 (2%) typhlitis, 104 of 208 (50%) colitis, 37 of 208 (18%) enterocolitis, 45 of 208 (22%) typhlocolitis, and 11 of 208 (5%) enterotyphlocolitis. We strongly recommend standardized testing of diarrheic horses during and/or after postmortem examination, as well as standardized reporting of histologic lesions in enterotyphlocolitis cases.

Alveolar macrophages (AMs) are the predominant innate immune cell in the distal respiratory tract. During inflammatory responses, AMs may be supplemented by blood monocytes, which differentiate into monocyte-derived macrophages (MDMs). Macrophages play important roles in a variety of common equine lower airway diseases, including severe equine asthma (SEA). In an experimental model, an inhaled mixture of Aspergillus fumigatus spores, lipopolysaccharide, and silica microspheres (FLS), induced SEA exacerbation in susceptible horses. However, whether equine AMs and MDMs have differing immunophenotypes and cytokine responses to FLS stimulation is unknown. To address these questions, alveolar macrophages/monocytes (AMMs) were isolated from bronchoalveolar lavage fluid and MDMs derived from blood of six healthy horses. Separately, AMMs and MDMs were cultured with and without FLS for six hours after which cell surface marker expression and cytokine production were analyzed by flow cytometry and a bead-based multiplex assay, respectively. Results showed that regardless of exposure conditions, AMMs had significantly higher surface expression of CD163 and CD206 than MDMs. Incubation with FLS induced secretion of IL-1β, IL-8, TNF-α and IFN-γ in AMMs, and IL-8, IL-10 and TNF-α in MDMs. These results suggest that AMMs have a greater proinflammatory response to in vitro FLS stimulation than MDMs, inferring differing roles in equine lung inflammation. Variability in recruitment and function of monocyte-macrophage populations warrant more detailed in vivo investigation in both homeostatic and diseased states.

Aquatic bird bornavirus 1 (ABBV-1) has a high prevalence of infection in certain North American populations of Canada geese ( Branta canadensis ), suggesting a possible role of these birds as an ABBV-1 reservoir. The goal of this study was to evaluate the ability of Canada geese to become experimentally infected with ABBV-1, develop lesions, and transmit the virus to conspecifics. One-week-old Canada geese ( n , 65) were inoculated with ABBV-1 through the intramuscular (IM) or cloacal (CL) routes, with the control group receiving carrier only. An additional 6 geese were added to each group to test horizontal transmission (sentinel birds). Geese were monitored daily, and selected birds were euthanized at 1, 8, and 15-weeks post infection (wpi) to assess virus replication in tissues and lesion development. At 15 wpi, over 70% of IM birds were infected, while the CL route yielded only 1 infected goose. Of the infected IM geese, 26% developed encephalitis and/or myelitis after 8 wpi. No clinical signs were observed, and no sentinel birds became infected in any group. Only 1 oropharyngeal swab (IM group) tested positive for ABBV-1 RNA, while the water from the enclosures was consistently negative for virus RNA. This study documents successful experimental infection of Canada geese with ABBV-1, with findings comparable to what is described in infection trials with other waterfowl species. However, minimal shedding and lack of environmental dispersal indicate that Canada geese have little potential to disseminate the virus among wild waterfowl, and that other species could be better suited to act as chronic ABBV-1 shedders in the wild.

Equine parvovirus-hepatitis (EqPV-H) was first reported from the serum and liver tissue of a horse diagnosed with Theiler's disease in the United States in 2018. Theiler's disease, also known as equine serum hepatitis, is a severe hepatitis with fulminant hepatic necrosis. The disease has most frequently been reported following the administration of equine-origin biological products; however, it has also been reported in in-contact horses with no prior biologic administration. EqPV-H has been detected in clinically healthy horses in North America (USA, Canada), Europe (Germany, Austria, Slovenia), Asia (China, South Korea), and South America (Brazil). Previous prevalence studies conducted worldwide have shown the presence of EqPV-H DNA in serum or plasma ranging from 3.2 to 19.8%. This study investigated the prevalence of EqPV-H DNA in 170 healthy broodmares of various breeds located on 37 farms in southern Ontario, Canada. The occurrence of EqPV-H infection was determined by quantitative PCR for EqPV-H DNA in serum samples. The effects of age, breed, season, pregnancy status, and equine herpesvirus-1 (EHV-1) vaccination history on EqPV-H status were also investigated. There was a prevalence of 15.9% (27/170) with viral loads of EqPV-H ranging from detectable to 2900 copies/mL. Statistical analysis showed that increasing age was a significant factor in the detection of EqPV-H DNA. Neither breed, season, pregnancy status, nor EHV-1 vaccination history was significant in predicting EqPV-H infection status.

Aquatic bird bornavirus 1 (ABBV-1) is a neurotropic virus that causes persistent infection in the nervous system of wild waterfowl. This study evaluated whether Pekin ducks, the most common waterfowl raised worldwide, are susceptible to ABBV-1 infection and associated disease. Groups of Pekin ducks were inoculated with ABBV-1 through the intracranial (IC; n, 32), intramuscular (IM; n, 30), and choanal (CH; n, 30) routes. Controls (CO; n, 29) received carrier only. At 1, 12, and 21 weeks postinfection (wpi), 7–14 birds were euthanized to assess virus distribution and lesions. Infection rates in the IC and IM groups were over 70%, while only 4 ducks in the CH group became infected. Neurological signs were observed in 8 ducks only, while over 25% of IC and IM birds had encephalitis and/or myelitis. Seroconversion was highest in the IC and IM groups, and mucosal ABBV-1 RNA shedding was most frequent in the IC group (53%). None of the fertile eggs laid during the experiment tested positive for ABBV-1 RNA. This study shows that Pekin ducks are permissive to ABBV-1 infection and partly susceptible to associated disease. While mucosal shedding may be an important route of transmission, congenital infection appears unlikely.

Although established as an important contributor to pig health and performance, high diversity and variability of the microbiome has challenged identification of a beneficial community composition that could inform best management practice and gut modifier development. To address this challenge, rectal swabs were collected at intervals from near birth to one-week postweaning from 4 piglets in 10 litters from 13 conventional and 9 RWA barns across Canada. The 16S rRNA gene was sequenced in 1,997 fecal samples collected at ~4 days of age (4d), 1 day before weaning (W-1), and 7 days after weaning (W+7), piglets were also weighed at the time of sampling. Raw sequences were denoised and assigned to genera using DADA2. After quality control and filtering there was an average of 32,710 reads per sample, with 649 genera identified in the samples. Principal Coordinate Analysis (PCoA) plots were created using the vegan and phyloseq packages (cao model and MDS settings). Relationships between metadata factors and the microbiome were investigated using PERMANOVA analysis in the adonis2 package. In PCoA plots samples clustered by production stage, with an expected marked change of the bacterial community following weaning. Because production stage had a large effect on the microbiome the effects of metadata factors were investigated within sampling visit. Metadata factors investigated included farrowing pen (FP) location at the 4 d-old sampling, barn and rearing system [conventional versus raised without antibiotics (RWA)] and the lifetime health (LH) status including always healthy, received a health score 1 or greater at any one visit or did not complete the study. At ~4 d of age, PERMANOVA indicated that all these factors were significantly linked to the microbiome composition (P = 0.001), FP explained the most microbiome variation (R2 = 0.338), followed by barn (R2 = 0.217). Rearing system and LH explained much less of the variation, R2 = 0.009 and R2 = 0.005, respectively. At W-1, the microbiome was not significantly correlated to LH (P = 0.053); however, the other metadata factors were significant (P = 0.001) with similar R2 values to the previous timepoint (FP; R2 = 0.317, barn R2 = 0.210, and system R2 = 0.008). At W+7 all metadata factors were once again significant (P < 0.005). The correlation to FP had reduced to R2 = 0.245, cohort increased to R2 = 0.266, system effects doubled to R2 = 0.21, and LH remained very low at R2 = 0.006. However, interactions between LH and FP (R2 = 0.059) and system and LH (R2=0.003) were also observed. These results suggest that farrowing pen has a significant and lasting effect on the microbiome. The effect of being raised RWA or conventionally was very small in preweaning piglets, but that affect increased post weaning. The immediate environment early in life appears to have a large effect on piglet microbiomes and may present an opportunity for beneficial intervention.

The SARS-CoV-2 pandemic is an ongoing threat to global health, and wide-scale vaccination is an efficient method to reduce morbidity and mortality. We designed and evaluated two DNA plasmid vaccines, based on the pIDV-II system, expressing the SARS-CoV-2 spike gene, with or without an immunogenic peptide, in mice, and in a Syrian hamster model of infection. Both vaccines demonstrated robust immunogenicity in BALB/c and C57BL/6 mice. Additionally, the shedding of infectious virus and the viral burden in the lungs was reduced in immunized hamsters. Moreover, high-titers of neutralizing antibodies with activity against multiple SARS-CoV-2 variants were generated in immunized animals. Vaccination also protected animals from weight loss during infection. Additionally, both vaccines were effective at reducing both pulmonary and extrapulmonary pathology in vaccinated animals. These data show the potential of a DNA vaccine for SARS-CoV-2 and suggest further investigation in large animal and human studies could be pursued.