Optimizing two-dose vaccine resource allocation to combat a pandemic in the context of limited supply: The case of COVID-19.

The adequate vaccination is a promising solution to mitigate the enormous socio-economic costs of the ongoing COVID-19 pandemic and allow us to return to normal pre-pandemic activity patterns. However, the vaccine supply shortage will be inevitable during the early stage of the vaccine rollout. Public health authorities face a crucial challenge in allocating scarce vaccines to maximize the benefits of vaccination. In this paper, we study a multi-period two-dose vaccine allocation problem when the vaccine supply is highly limited. To address this problem, we constructed a novel age-structured compartmental model to capture COVID-19 transmission and formulated as a nonlinear programming (NLP) model to minimize the total number of deaths in the population. In the NLP model, we explicitly take into account the two-dose vaccination procedure and several important epidemiologic features of COVID-19, such as pre-symptomatic and asymptomatic transmission, as well as group heterogeneity in susceptibility, symptom rates, severity, etc. We validated the applicability of the proposed model using a real case of the 2021 COVID-19 vaccination campaign in the Midlands of England. We conducted comparative studies to demonstrate the superiority of our method. Our numerical results show that prioritizing the allocation of vaccine resources to older age groups is a robust strategy to prevent more subsequent deaths. In addition, we show that releasing more vaccine doses for first-dose recipients could lead to a greater vaccination benefit than holding back second doses. We also find that it is necessary to maintain appropriate non-pharmaceutical interventions (NPIs) during the vaccination rollout, especially in low-resource settings. Furthermore, our analysis indicates that starting vaccination as soon as possible is able to markedly alleviate the epidemic impact when the vaccine resources are limited but are currently available. Our model provides an effective tool to assist policymakers in developing adaptive COVID-19 likewise vaccination strategies for better preparedness against future pandemic threats.

The 100 Most-Cited Articles in COVID-19 Vaccine Hesitancy Based on Web of Science: A Bibliometric Analysis.

Purpose: To perform a bibliometric analysis of the 100 most-cited articles (T100 articles) on COVID-19 vaccine hesitancy to characterize current trends. Methods: The data of the bibliometric analysis were retrieved from the Web of Science Core Collection (WoSCC) database on January 29, 2023, and the results were sorted in descending order by citations. Two researchers independently extracted the characteristics of the top 100 cited articles, including title, author, citations, publication year, institution, country, author keywords, Journal Cited Rank, and impact factor. Excel and VOSviewer were used to analyze the data. Results: The T100 articles ranged from 79 to 1125 citations, with a mean of 208.75. The T100 articles were contributed by 29 countries worldwide, of which the USA ranked first with 28 articles and 5417 citations. The T100 articles were published in 61 journals; the top three citations were VACCINES, NATURE MEDICINE, and EUROPEAN JOURNAL OF EPIDEMIOLOGY, and the number of citations was 2690, 1712, and 1644, respectively. Professor Sallam, M(n=4) from Jordan, is the author who participated in the most published articles. Catholic University of the Sacred Heart (n=8) had the most T100 articles. Conclusion: It is the first bibliometric analysis of the T100 articles in the field of COVID-19 vaccine hesitancy. We carefully analyzed and described the characteristics of these T100 articles, which provide ideas for further strengthening COVID-19 vaccination and fighting against the epidemic in the future.

A closer look at the experiences of international graduate students during the COVID-19 pandemic: Connections to wellbeing

Graduate education, especially at the doctoral level, provides students with opportunities to learn, grow, and gain independence as scholars, as well as gives rise to a certain degree of stress. The stress level that the program itself generates as a matter of course scales up with additional challenges for some graduate students, including deficient academic engagement or, in some cases, poor relationships with their supervisors. Other additional stressors can be counted, like a reverted work-life balance, financial difficulties, a lack of permanent employment, the pressure to publish in high-impact journals and participate in conferences or congresses, and the feeling of an uncertain future. This chapter is a collaborative autoethnographic study seeking to explore the authors experiences as international doctoral students leading transnational lives in Canada. They are three international Turkish, Chinese, and Vietnamese doctoral students in a Joint Ph.D. in Educational Studies program at a Canadian university. Acknowledging the diverse demographic backgrounds-including gender, race, ethnicity, and class-the chapter aims to situate the collaboration in a critical discussion on different challenges the authors faced and resources they used while learning and sustaining doctoral studies amidst a global crisis, which are emerging themes in their findings. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein.

Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and GD (GI-7), and the corresponding region of M41 (GI-1), as the minimal SABD using truncated protein histochemistry and neuraminidase assays. Both α-2,3- and α-2,6-linked sialic acids on the surfaces of CEK cells can be used as attachment receptors by IBV, leading to increased infection efficiency. However, 9-O acetylation of the sialic acid glycerol side chain inhibits IBV S1 and SABD protein binding. We further constructed recombinant strains in which the S1 gene or the SABD in the GD and SD genomes were replaced with the corresponding region from M41 by reverse genetics. Infecting chickens with these viruses revealed that the virulence and nephrotropism of rSDM41-S1, rSDM41-206, rGDM41-S1, and rGDM41-206 strains were decreased to various degrees compared to their parental strains. A positive sera cross-neutralization test showed that the serotypes were changed for the recombinant viruses. Our results provide insight into IBV infection of host cells that may aid vaccine design. IMPORTANCE To date, only α-2,3-linked sialic acid has been identified as a potential host binding receptor for IBV. Here, we show the minimum region constituting the sialic acid binding domain (SABD) and the binding characteristics of the S1 subunit of spike (S) protein of IBV strains SD (GI-19), GD (GI-7), and M41 (GI-1) to various sialic acids. The 9-O acetylation modification partially inhibits IBV from binding to sialic acid, while the virus can also bind to sialic acid molecules linked to host cells through an α-2,6 linkage, serving as another receptor determinant. Substitution of the putative SABD from strain M41 into strains SD and GD resulted in reduced virulence, nephrotropism, and a serotype switch. These findings suggest that sialic acid binding has diversified during the evolution of γ-coronaviruses, impacting the biological properties of IBV strains. Our results offer insight into the mechanisms by which IBV invades host cells.

An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of Omicron BA.1, BA.1.1, BA.2 and BA.3 from an atlas of 50 monoclonal antibodies (mAbs), covering seven epitope classes of the SARS-CoV-2 receptor-binding domain (RBD). Here, we update the atlas of totally 77 mAbs against emerging sub-variants including BQ.1.1 and XBB and find that BA.4/5, BQ.1.1 and XBB display further evasion. Besides, investigation into the correlation of binding and neutralization of mAbs reveals the important role of antigenic conformation in mAb functioning. Moreover, the complex structures of BA.2 RBD/BD-604/S304 and BA.4/5 RBD/BD-604/S304/S309 further elucidate the molecular mechanism of antibody evasion by these sub-variants. By focusing on the identified broadly potent mAbs, we find a general hotspot epitope on the RBD, which could guide the design of vaccines and calls for new broad-spectrum countermeasures against COVID-19. Graphical Immune evasion of SARS-CoV-2 variants needs to be monitored continuously. He et al. assess the efficacy of 77 neutralizing mAbs against recently emerging Omicron sub-variants including BQ.1.1 and XBB. They reveal the binding-neutralization correlation of mAbs and point out a hotspot epitope targeting by broadly neutralizing antibodies.

COVID-19 vaccine booster dose hesitancy among key groups: A cross-sectional study.

Vaccination is an important tool for controlling the spread of coronavirus disease. Notably, it is important to achieve higher vaccine booster coverage across key groups - including front-line workers who could be exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and those who live and work in crowded places - to prevent or reduce the risk of severe infection and poor disease outcomes. The purpose of the study was to understand the COVID-19 vaccine booster hesitancy among key groups in Luzhou, China, to analyze its influencing factors, and to provide scientific basis and theoretical guidance for the implementation of targeted intervention. Guided by the "3Cs" model, a self-designed questionnaire was prepared through a literature search using the Delphi method. All questionnaires were completed online through a QR code. Among the 548 participants, 173 had vaccine hesitation, accounting for 31.6%. Indeed, the scores for perceived safety, expected vaccine effectiveness, and trust in the vaccine delivery system were all lower in the hesitance group than in the non-hesitance group. However, the scores for low necessity were higher in the hesitance group. The factors influencing booster hesitancy were examined, and the probability of hesitancy decreased by 72.2% and 62.5% for every 1-point increase in the confidence and safety scores, respectively. Meanwhile, the probability of hesitancy increased by 25.8% for every 1-point increase in the low necessity score. Although the COVID-19 vaccine booster hesitancy reported in the study was relatively low, a large gap remains in the willingness to receive COVID-19 vaccination in China. Therefore, the state and relevant departments should take targeted measures to help reduce vaccine hesitancy among the public and enable smooth progress in the large-scale COVID-19 vaccine booster campaign in the future.

An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB.

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of Omicron BA.1, BA.1.1, BA.2, and BA.3 from an atlas of 50 monoclonal antibodies (mAbs), covering seven epitope classes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update the atlas of totally 77 mAbs against emerging sub-variants including BQ.1.1 and XBB and find that BA.4/5, BQ.1.1, and XBB display further evasion. Besides, investigation into the correlation of binding and neutralization of mAbs reveals the important role of antigenic conformation in mAb functioning. Moreover, the complex structures of BA.2 RBD/BD-604/S304 and BA.4/5 RBD/BD-604/S304/S309 further elucidate the molecular mechanism of antibody evasion by these sub-variants. By focusing on the identified broadly potent mAbs, we find a general hotspot epitope on the RBD, which could guide the design of vaccines and calls for new broad-spectrum countermeasures against COVID-19.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants.

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.

A comparative study of positive and negative electronic word-of-mouth on the SERVQUAL scale during the COVID-19 epidemic - taking a regional teaching hospital in Taiwan as an example.

BACKGROUND: In recent years, studies have shown that electronic WOM (eWOM) directly reflects consumers' post-purchase psychological perception and directly affects repurchase behavior. This information is valued by institutions in various fields. Within the scope of the evaluation of service characteristics, medical service is the least visible and most difficult service attribute to evaluate. Service organizations must have high trust attributes. Therefore, an eWOM review significantly influences people's decision-making process when choosing a healthcare provider. The purpose of this research is to combine eWOM reviews with the SERVQUAL scale in a comparative study of positive and negative eWOM reviews of a regional teaching hospital in Taiwan. METHODS: This research obtained data from publicly available eWOM reviews on Google Maps of a regional teaching hospital in Taiwan over the past 10 years (from June 24, 2011, to December 31, 2021) using website scraping technology. The semantic content analysis method was used in this study to classify eWOM reviews according to the revised PZB SERVQUAL scale. RESULTS: Statistical analysis was conducted. During the COVID-19 pandemic, positive reviews showed a downward trend. Among the five determinants of the SERVQUAL of PZB, positive eWOM reviews performed best in "assurance" with a positive review rate of 60.00%, followed by 42.11% for "reliability". For negative eWOM reviews, "assurance" performed the worst with a positive rate of 72.34%, followed by "responsiveness" at 28.37% and "reliability" at 26.95%. CONCLUSION: Since the onset of COVID-19 in 2020, negative eWOM has increased significantly and exceeded the amount of positive eWOM. Regardless of positive and negative reviews, what patients care most about is "assurance" of the professional attitude and skills of medical staff, which urgently needs to be strengthened. In addition, good "reliability" will help to develop positive eWOM. However, "responsiveness" as indicated by poor service waiting time can easily lead to the spread of negative eWOM. Hospital management should focus on these service-oriented qualities.

Does COVID-19 Affect the Accessibility of Outdoor Sports Venues? A Case Study in Nanchang, China

The COVID-19 pandemic has been a great challenge to society, the economy, and population health. It has become a significant public health event and social problem. Exploring the impact of COVID-19 on the accessibility of outdoor sports venues is crucial for people's health. Based on spatial theory, the quantitative and qualitative analyses of outdoor sports venues' spatial distribution and accessibility were conducted, and the epidemic's impact on them was analyzed. The results show that: (1) The existing outdoor sports venues in Nanchang show a distribution pattern of 'sparse in the north and south, and strong aggregation in the middle';. (2) As a result of the epidemic, the center of the standard deviation ellipse in outdoor sports sites shifted to the southeast, while the number of open venues decreased by 68%. (3) Before COVID-19, the entire study area could achieve full coverage by driving for 17 min, riding for 70 min, or walking for 119 min. After COVID-19, the time increased to 29, 109, and 193 min, respectively. (4) Under the high-risk scenario of COVID-19, the average walking time for people to reach outdoor sports venues increased from 6.2 min to 14.0 min in the study area, with an increase of 126%. Finally, according to the findings of this study, recommendations were made on how government departments could build or re-open outdoor sports venues during and after this epidemic.

Comparison of the Performance of 24 Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in the Diagnosis of Coronavirus Disease 2019 Patients.

Background: The accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control Coronavirus Disease-2019 (COVID-19). The performance of different antibody detection methods for diagnosis of COVID-19 is inconclusive. Methods: Between 16 February and 28 February 2020, 384 confirmed COVID-19 patients and 142 healthy controls were recruited. 24 different serological tests, including 4 enzyme-linked immunosorbent assays (EIAs), 10 chemiluminescent immunoassays (CLIAs), and 10 lateral flow immunoassays (LFIAs), were simultaneously performed. Results: The sensitivities of anti-SARS-CoV-2 IgG and IgM antibodies with different reagents ranged from 75 to 95.83% and 46.09 to 92.45%, respectively. The specificities of both anti-SARS-CoV-2 IgG and IgM were relatively high and comparable among different reagents, ranged from 88.03 to 100%. The area under the curves (AUCs) of different tests ranged from 0.733 to 0.984, and the AUCs of EIAs or CLIAs were significantly higher than those of LFIAs. The sensitivities of both IgG and IgM gradually increased with increase of onset time. After 3-4 weeks, the sensitivities of anti-SARS-CoV-2 IgG were maintained at a certain level but the sensitivities of IgM were gradually decreased. Six COVID-19 patients who displayed negative anti-SARS-CoV-2 results were associated with the factors such as older age, having underlying diseases, and using immunosuppressant. Conclusion: Besides the purpose of assessing the impact of the SARS-CoV-2 pandemic in the population, SARS-CoV-2 antibody assays may have an adjunct role in the diagnosis and exclusion of COVID-19, especially by using high-throughput technologies (EIAs or CLIAs).

The choice of Taiwanese college students to vaccinate against severe special infectious pneumonia COVID-19 based on the integrated theory of planning behavior.

Taiwan's coronavirus (COVID-19) vaccine procurement was delayed until October 2021. With the vaccine's introduction in Taiwan, the public will have an opportunity to choose vaccination. Choosing to vaccinate involves considerations regarding the trade-off between the protective power of the vaccine and its side effects, which is a planned behavior. College students have considered high-risk objects for COVID-19 outbreaks given their lifestyle, and their efficient vaccination may help reduce mutual infection between college students and the general public. This study obtained 707 valid questionnaires from Taiwan college students (20 years old and above). We investigated several factors during our college students' survey regarding vaccination. Among this integrated TPB model, "Attitude," "Subjective Norm," "Perceived Behavioral Control," and "COVID-19 Information Asymmetry" had a positive impact on vaccination "Behavioral Intention." COVID-19 information asymmetry positively and significantly affected behavioral intention through perceived behavioral control, while perceived behavioral control had a mediating effect. To promote the behavioral intention of college students to choose COVID-19 vaccination, public and private departments for epidemic prevention must aim to overcome the self-efficacy barriers of perceived behavioral control and promote the primary group influence effect of subjective norm and the self-interest factor of attitude. Governments and NGOs should also ensure prompt and accurate transmission of epidemic and vaccine information and actively investigate and prohibit misleading details from unknown sources and no scientific basis. Such a policy will generate trust, effectively increasing the vaccination rate and reducing cluster infection.

Electron beam technology for Re-processing of personal protective equipment.

Beginning with the outbreak of COVID-19 at the dawn of 2020, the continuing spread of the pandemic has challenged the healthcare market and the supply chain of Personal Protective Equipment (PPE) around the world. Moreover, the emergence of the variants of COVID-19 occurring in waves threatens the sufficient supply of PPE. Among the various types of PPE, N95 Respirators, surgical masks, and medical gowns are the most consumed and thus have a high potential for a serious shortage during such emergencies. Considering the unanticipated demand for PPE during a pandemic, re-processing of used PPE is one approach to continue to protect the health of first responders and healthcare personnel. This paper evaluates the viability and efficacy of using FDA-approved electron beam (eBeam) sterilization technology (ISO 11137) to re-process used PPE. PPEs including 3M N95 Respirators, Proxima Sirus gowns, and face shields were eBeam irradiated in different media (air, argon) over a dose range of 0-200 kGy. Several tests were then performed to examine surface properties, mechanical properties, functionality performance, discoloration phenomenon, and liquid barrier performance. The results show a reduction of filtration efficiency to about 63.6% in the N95 Respirator; however, charge regeneration may improve the re-processed efficiency. Additionally, mechanical degradation was observed in Proxima Sirus gown with increasing dose up to 100 kGy. However, no mechanical degradation was observed in the face shields after 10 times donning and doffing. Apart from the face shield, N95 Respirators and Proxima Sirus gown both show significant mechanical degradation with ebeam dose over sterilization doses (>25 kGy), indicating that eBeam technology is not appropriate for the re-processing these PPEs.

Electron beam technology for Re-processing of personal protective equipment

Beginning with the outbreak of COVID-19 at the dawn of 2020, the continuing spread of the pandemic has challenged the healthcare market and the supply chain of Personal Protective Equipment (PPE) around the world. Moreover, the emergence of the variants of COVID-19 occurring in waves threatens the sufficient supply of PPE. Among the various types of PPE, N95 Respirators, surgical masks, and medical gowns are the most consumed and thus have a high potential for a serious shortage during such emergencies. Considering the unanticipated demand for PPE during a pandemic, re-processing of used PPE is one approach to continue to protect the health of first responders and healthcare personnel. This paper evaluates the viability and efficacy of using FDA-approved electron beam (eBeam) sterilization technology (ISO 11137) to re-process used PPE. PPEs including 3M N95 Respirators, Proxima Sirus gowns, and face shields were eBeam irradiated in different media (air, argon) over a dose range of 0–200 kGy. Several tests were then performed to examine surface properties, mechanical properties, functionality performance, discoloration phenomenon, and liquid barrier performance. The results show a reduction of filtration efficiency to about 63.6% in the N95 Respirator;however, charge regeneration may improve the re-processed efficiency. Additionally, mechanical degradation was observed in Proxima Sirus gown with increasing dose up to 100 kGy. However, no mechanical degradation was observed in the face shields after 10 times donning and doffing. Apart from the face shield, N95 Respirators and Proxima Sirus gown both show significant mechanical degradation with ebeam dose over sterilization doses (>25 kGy), indicating that eBeam technology is not appropriate for the re-processing these PPEs.

Comparison of the Performance of 24 Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in the Diagnosis of Coronavirus Disease 2019 Patients

Background The accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control Coronavirus Disease-2019 (COVID-19). The performance of different antibody detection methods for diagnosis of COVID-19 is inconclusive. Methods Between 16 February and 28 February 2020, 384 confirmed COVID-19 patients and 142 healthy controls were recruited. 24 different serological tests, including 4 enzyme-linked immunosorbent assays (EIAs), 10 chemiluminescent immunoassays (CLIAs), and 10 lateral flow immunoassays (LFIAs), were simultaneously performed. Results The sensitivities of anti-SARS-CoV-2 IgG and IgM antibodies with different reagents ranged from 75 to 95.83% and 46.09 to 92.45%, respectively. The specificities of both anti-SARS-CoV-2 IgG and IgM were relatively high and comparable among different reagents, ranged from 88.03 to 100%. The area under the curves (AUCs) of different tests ranged from 0.733 to 0.984, and the AUCs of EIAs or CLIAs were significantly higher than those of LFIAs. The sensitivities of both IgG and IgM gradually increased with increase of onset time. After 3–4 weeks, the sensitivities of anti-SARS-CoV-2 IgG were maintained at a certain level but the sensitivities of IgM were gradually decreased. Six COVID-19 patients who displayed negative anti-SARS-CoV-2 results were associated with the factors such as older age, having underlying diseases, and using immunosuppressant. Conclusion Besides the purpose of assessing the impact of the SARS-CoV-2 pandemic in the population, SARS-CoV-2 antibody assays may have an adjunct role in the diagnosis and exclusion of COVID-19, especially by using high-throughput technologies (EIAs or CLIAs).

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.

Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism.

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3.

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.

Role of Stress Granules in Suppressing Viral Replication by the Infectious Bronchitis Virus Endoribonuclease.

Infectious bronchitis virus (IBV), a γ-coronavirus, causes the economically important poultry disease infectious bronchitis. Cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation. Previous studies suggested that SGs were involved in the antiviral activity of host cells to limit viral propagation. Here, we aimed to delineate the molecular mechanisms regulating the SG response to pathogenic IBV strain infection. We found that most chicken embryo kidney (CEK) cells formed no SGs during IBV infection and IBV replication inhibited arsenite-induced SG formation. This inhibition was not caused by changes in the integrity or abundance of SG proteins during infection. IBV nonstructural protein 15 (Nsp15) endoribonuclease activity suppressed SG formation. Regardless of whether Nsp15 was expressed alone, with recombinant viral infection with Newcastle disease virus as a vector, or with EndoU-deficient IBV, the Nsp15 endoribonuclease activity was the main factor inhibiting SG formation. Importantly, uridine-specific endoribonuclease (EndoU)-deficient IBV infection induced colocalization of IBV N protein/dsRNA and SG-associated protein TIA1 in infected cells. Additionally, overexpressing TIA1 in CEK cells suppressed IBV replication and may be a potential antiviral factor for impairing viral replication. These data provide a novel foundation for future investigations of the mechanisms by which coronavirus endoribonuclease activity affects viral replication. IMPORTANCE Endoribonuclease is conserved in coronaviruses and affects viral replication and pathogenicity. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal, and reproductive systems, causing millions of dollars in lost revenue to the poultry industry worldwide annually. Mutating the viral endoribonuclease poly(U) resulted in SG formation, and TIA1 protein colocalized with the viral N protein and dsRNA, thus damaging IBV replication. These results suggest a new antiviral target design strategy for coronaviruses.

Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.