Journal Article

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

Pouriayevali, Mohammad Hassan, Bahmanjeh, Anahita, Salehi-Vaziri, Mostafa, Sabouni, Talieh, Doroud, Delaram, Kadkhodazadeh, Maryam, Biglari, Alireza, Shahali, Maryam, Esmaeili, Saber, Verez-Bencomo, Vicente, Panahi, Mohammad, Khoshroo, Fereidoon, Garcia-Rivera, Dagmar, Teimoori, Ali, Khosravi, Mohammad Ali, Valdes-Balbin, Yury, Abdoli, Asghar, Baesi, Kazem

2022

Overview

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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adenovector / Adenoviridae / Adenoviruses / Allergy and Immunology / Animal models / Animals / Antibodies / Cell-mediated immunity / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 infection / COVID-19 vaccines / Cytokines / Cytomegalovirus / Dimers / Disease control / Experiments / Expression vectors / Hamsters / Herd immunity / Human tissues / humans / Humoral immunity / immune response / Immunity / Immunogenicity / Immunoglobulin G / Iran / lungs / Mice / nucleoproteins / pandemic / Pandemics / Pharynx / Protection / Proteins / Rabbits / Rodents / Safety / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Spike protein / t-Plasminogen activator / Thrombolytic drugs / Tissue Plasminogen Activator / Toxicity / Tumor necrosis factor-TNF / vaccination / Vaccine / Vaccines / Viral diseases / Viral Vaccines / Viruses