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BackgroundDespite numerous genetic studies on Infectious Bronchitis Virus (IBV), many strains from the Middle East remain misclassified or unclassified. Genotype 1 (GI-1) is found globally, while genotype 23 (GI-23) has emerged as the predominant genotype in the Middle East region, evolving continuously through inter- and intra-genotypic recombination. The GI-23 genotype is now enzootic in Europe and Asia.MethodsOver a 24-month period from May 2022 to June 2024, 360 samples were collected from 19 layer and 3 broiler poultry farms in central Saudi Arabia. The chickens exhibited reduced laying rates and symptoms such as weakness and respiratory distress, while broilers showed respiratory issues. Samples, including tracheal swabs and various tissue specimens, were pooled, homogenized, and stored at -20 °C prior to PCR analysis. The samples underwent virus isolation in embryonated chicken eggs, RNA extraction using automated systems, and detection of IBV through real-time RT-PCR targeting a conserved 5’-UTR fragment. Full-length genome sequencing was performed, and recombination analysis was conducted using RDP 4.6.ResultsSaudi IBV strains were found to cluster into genotypes GI-1 and GI-23.1. The study identified critical amino acid substitutions in the hypervariable regions of the spike protein and detected recombination events in the ORF1ab, N, M, 3ab, and 5ab genes, with nsp3 of the ORF1ab showing the greatest number of recombination events.ConclusionThe multiple inter- and intra-genotypic recombination events that were detected in different genes indicate that the circulating IBV strains do not share a single ancestor but have emerged through successive recombination events.

NRC publication: Yes

Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

The appearance of several variants of concern (VOCs) of SARS-CoV-2 affects the efficacy of currently available vaccines and causes continuous spread and reinfection between humans. These variants possess different spike (S) protein mutations, which could affect viral pathogenicity, transmission, and immune escape. Herein, we develop a synthetic codon-optimized DNA vaccine (VIU-1007) expressing full-length S protein. The developed vaccine is stabilized by two K986P and V987P proline substitutions and resistant to cleavage by proteases such as furin by deletion of arginine residues (R682, R683, and R685) in multibasic furin cleavage site (RRAR). Additionally, it carries K417N, E484K, N501Y, and D614G substitutions in the receptor binding domain (RBD) derived from the beta VOC. Following the validation and characterization of the in vitro S protein expression, the humoral and cellular immunogenicity of VIU-1007 was assessed in immunized Balb/c mice. While both regimens elicited a Th-1-biased immune response based on S1-specific binding IgG isotypes, three vaccine doses significantly enhanced IgG levels. Furthermore, CD4+ and CD8+ memory T cell responses in spleens and draining inguinal lymph nodes were significantly higher in mice received three doses of VIU-1007 when compared to those received two doses only. Importantly, sera from mice immunized with three doses showed broad neutralization breadth against several SARS-CoV-2 variants, including alpha, beta, gamma, delta, and omicron VOCs. Moreover, the sera showed limited neutralization capacity against SARS-CoV-1, Bat SARS-like coronavirus WIV1, and MERS-CoV. Together, while these data suggest the presence of common neutralizing-rich epitopes between SARS-CoV-2 variants and some other betacoronaviruses, the ongoing evolution of SARS-CoV-2 could result in escape from vaccine-induced immunity, which requires a continuous update of vaccines.

Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic human coronaviruses (CoVs). Anti-CoVs mAbs and vaccines may be effective, but the emergence of neutralization escape variants is inevitable. Angiotensin-converting enzyme 2 and dipeptidyl peptidase 4 enzyme are the getaway receptors for SARS-CoV-2 and MERS-CoV, respectively. Thus, we reformatted these receptors as Fc-fusion decoy receptors. Then, we tested them in parallel with anti-SARS-CoV (ab1-IgG) and anti-MERS-CoV (M336-IgG) mAbs against several variants using pseudovirus neutralization assay. The generated Fc-based decoy receptors exhibited a strong inhibitory effect against all pseudotyped CoVs. Results showed that although mAbs can be effective antiviral drugs, they might rapidly lose their efficacy against highly mutated viruses. We suggest that receptor traps can be engineered as Fc-fusion proteins for highly mutating viruses with known entry receptors, for a faster and effective therapeutic response even against virus harboring antibodies escape mutations. Statement of Significance: Decoy receptors can be effective against infectious diseases once their gateway receptors are identified. In our report, we showed that ACE2-Fc and DPP4-Fc were able to inhibit pseudotyped SARS-CoV-2 and MERS-CoV variants. Therefore, antibody-like receptor traps can act as potential therapeutics for highly mutated viruses.