Mazen Hassanain

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.

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.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

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.

Purpose: Over the last decades, the incidence of pancreatic cancer has increased, particularly in countries with a higher socioeconomic status. The present work aimed to provide detailed epidemiological data on the incidence of pancreatic cancer in Saudi Arabia. Patients and Methods: In this retrospective descriptive study, the epidemiological data on pancreatic cancer cases diagnosed in 13 administrative regions of Saudi Arabia between January 2004 and December 2015 were extracted from the Saudi Cancer Registry. The frequency, the crude incidence rate (CIR), and the age-standardized incidence rate (ASIR), stratified by geographical region, gender, and the year of diagnosis, were analyzed. Results: From January 2004 to December 2015, a total of 2338 cases of pancreatic cancer were registered, including 1443 males and 895 females. The overall CIR was 1.28/100,000 among males and 0.80/100,000 in females, with an overall ASIR of 2.26 and 1.41/100,000 for males and females, respectively. Higher ASIR and CIR were observed among males than females (ratio 1.6). In both genders, the ASIR of pancreatic cancer increased with increasing age, with the highest incidence in patients aged 70 years or more. The ASIR in the Eastern Region (3.2/100,000) and the regions of Riyadh (3.0/100,000) and Tabuk (2.6/100,000) proved to be significantly higher than in the other regions of the country. Among women, the ASIR was significantly higher in Riyadh (2.3/100,000), the northern region (2.2/100,000), and Tabuk (2.0/100,000). Conclusion: This study revealed a slight increase of the CIR and ASIR of pancreatic cancer among males and females of the Saudi population. Eastern region, Riyadh, and Tabuk had the highest overall ASIRs of pancreatic cancer among males, Riyadh, Northern region, and Tabuk among Saudi females. The area least affected by pancreatic cancer was observed in Jazan among male and female Saudis. The rates of pancreatic cancer in Saudi Arabia were significantly higher among males compared with female Saudis. Further analytical studies are needed to identify the potential risk factors for pancreatic cancer among the Saudi population.