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.

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

“…Similar to our study, this vaccination did not affect viral shedding in pharyngeal swabs but did reduce weight loss over the course of infection. In contrast to our study, the nCoV-S(JET) did induce neutralizing antibodies and decreased areas of consolidation and SARS-CoV-2 RNA labeling in areas of inflammation in the lung [ 36 ]. The distinct outcomes in our study with those of nCoV-S(JET) study suggest that neutralizing antibodies may play an important role in diminishing COVID-19 disease progression.…”

“…Our study and others evaluating DNA-vaccines [ 36 ] supports the need for boosting to achieve significant antibody titer increase [ 27 , 36 ], an important public health consideration for deployment of vaccines against SARS-CoV-2 [ 27 ]. Alternative vaccine platforms may provide significant protection against COVID-19 after just a single vaccination.…”

Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines

“…The hACE2 transgenic hamsters used here also provide a new and relevant model of severe/fatal SARS CoV-2 disease that can be utilized to test vaccines and therapeutics 25 . Consistent with other studies of hamsters, other experimental animals and potentially humans [29][30][31][32] , protection from severe disease was not closely associated with an effect on oropharyngeal swab titers; however, if control and SAb-185 treated animals that had delayed virus replication were removed, suppression of titers by SAb 185 was significant for combined challenge groups (p=0.02) on D5 post challenge. This contributes to the body of evidence that vaccination and/or Ab therapeutic treatment may only provide limited protection from virus infection and upper respiratory tract replication.…”

Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge

“…Macaques, especially Macaca mulatta appears to be the most susceptible to SARS-CoV-2; they developed COVID-19-like lung lesions albeit with moderate symptoms [32]. Presently, aged Rhesus macaques [33,34], baboons [35], hamsters [30,36] and mice [7À9,14] developed more severe disease (versus young) ranging from weight loss, exacerbated pneumonia, cellular pulmonary infiltration and Favipiravir, HCQ/azithromycin [52] Neutralizing mAb [55, 174, 191À195] Ranitidine bismuth citrate [196] Vaccine [62,165,197] Tree shrew [23,24] Low-to-high, Age-dependent susceptibility similar [49] Neutralizing mAb [17,192] Convalescent plasma & Remdesivir [16,37,54] Baicalein [198] Dalbavancin [162] interferon-λ1a [9] Vaccine [8,9,64,165,199] Plitidepsin [50] Cat [25,26] High cytokine release to respiratory dysfunction. Notably, one mouse study reported hyposmia/anosmia after intranasal SARS-CoV-2 inoculation [37].…”