6/22/2023 0 Comments Protein shedding from vaccineGiven its critical role in virus entry, the S RBD is also a major target of host responses to SARS-CoV-2, thus representing a good target for subunit vaccine development.Īs of July 15, 2022, there are two mRNA vaccines (Pfizer/BNT162b2 and Moderna/mRNA-1273) and one recombinant-adenovirus-vectored vaccine (Janssen vaccine/) approved by the U.S. The virus-host receptor interaction occurs between the main functional motif of S within the receptor-binding domain (RBD), known as the receptor-binding motif (RBM), which is present at the tip of the trimer of the viral S protein, and the host cell receptor, ACE2. The S protein mediates SARS-CoV-2 entry into target cells by initially binding to angiotensin-converting enzyme 2 (ACE2) on the host cell surface (via the S1 domain) and subsequently fusing (via the S2 domain) the viral membrane with a host membrane. The virus encodes a major surface glycoprotein, the spike (S) protein, which mediates receptor binding and is the main target of host immune responses. SARS-CoV-2 belongs to the subgenus Sarbecovirus, genus Betacoronavirus of the family Coronaviridae and is an enveloped positive-strand RNA virus. However, the genetic distance of approximately 4% (~ 1,150 mutations) between RaTG13 and SARS-CoV-2 isolate Wuhan-Hu-1 indicates that transmission likely did not occur directly from bats to humans and further suggests that a yet-unidentified animal species may have served as an intermediate host prior to spillover of the virus into humans. The betacoronavirus RaTG13, isolated from the bat species Rhinolophus affinis, was found to be the animal coronavirus most closely related to SARS-CoV-2, sharing over 96% identity at the whole-genome level. Following the initial reports, human-to-human transmission was confirmed as individuals began to contract the infection without ever having been at the seafood market. The earliest reports of COVID-19 were linked to the Huanan Seafood Wholesale Market in Wuhan, China, which sold aquatic animals, live poultry, and several wild animal species. By March 2023, the World Health Organization (WHO) officially registered more than 760 million confirmed cases and over 6.8 million deaths worldwide caused by the coronavirus disease 2019 (COVID-19) pandemic ( ). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent of one of the deadliest pandemics of the last 100 years. Most importantly, vaccination significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model. Additionally, the vaccine elicited neutralizing antibodies and T cell responses on day 42 post-immunization using a low dose of the linear DNA construct in a prime-boost regimen. The linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects. Here, we evaluate the safety, immunogenicity, and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. Importantly, in vivo DNA delivery combined with electroporation (EP) has been used successfully in the field of veterinary oncology, resulting in high rates of response after electrochemotherapy. However, the efficiency of DNA vaccination needs to be improved for use in humans. Additionally, DNA vaccines efficiently induce both B- and T-cell responses by expressing the antigen within transfected host cells, and the antigen, after being processed into peptides, can associate with MHC class I or II of antigen-presenting cells (APCs) to stimulate different T cell responses. The versatility, low cost, and rapid production of DNA vaccines provide important advantages over other platforms. Currently, two mRNA-based vaccines and one adenovirus-vectored vaccine have been approved and are available for use in the U.S. Vaccination has been the main strategy used to contain the spread of the virus and to prevent hospitalizations and deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 760 million cases and over 6.8 million deaths as of March 2023.
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