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Potency, toxicity and protection evaluation of PastoCoAd candidate vaccines: Novel preclinical mix and match rAd5 S, rAd5 RBD-N and SOBERANA dimeric-RBD protein.

Vaccine | 2022

Despite substantial efforts, no effective treatment has been discovered for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. Therefore, vaccination to reach herd immunity is the ultimate solution to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate the potency, toxicity, and protection of candidate PastoCoAd vaccines as novel mix and match of recombinant adenovirus type 5 (rAd5) containing the full-length spike protein (rAd5-S), rAd5 containing the receptor-binding domain of S protein and nucleoprotein (rAd5 RBD-N), and SOBERANA dimeric RBD protein of SARS-CoV-2. Three vaccine candidates were developed against SARS-CoV-2 using adenoviral vectors, including the prime-boost (rAd5-S/rAd5 RBD-N), heterologous prime-boost (rAd5-S/ SOBERANA vaccine), and prime only (mixture of rAd5-S and rAd5 RBD-N). The rAd5-S and rAd5 RBD-N were produced with a Cytomegalovirus promoter and the human tissue plasminogen activator (tPA) leader sequence. The immunogenicity of vaccine candidates was also evaluated in mouse, rabbit, and hamster models and protection was evaluated in a hamster model. Following the injection of vaccine candidates, no significant toxicity was observed in the tissues of animal models. The immunogenicity studies of mice, rabbits, and hamsters showed that responses of total IgG antibodies were significantly higher with the prime-only and heterologous prime-boost vaccines as compared to the other groups (P < 0.009). Virus neutralizing antibodies were detected, and the level of cytokines related to humoral and cellular immunity increased significantly in all vaccinated models. A high cellular immunity response was found in the vaccinated groups compared to the controls. On the other hand, the vaccine challenge test showed that the virus titers significantly decreased in the pharynx and lung tissues of vaccinated hamsters compared to the control group. These successful findings suggest the safety and protection produced by the heterologous prime-boost vaccine (adenovector/ SOBERANA RBD), as well as a single dose of adenovector vaccine in animal models.

Pubmed ID: 35393148 RIS Download

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GenBank (tool)

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NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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