Retraction: Sung et al. Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate. Vaccines 2022, 10, 2.

The journal retracts the article "Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate"[...].

Safety and Immunogenicity of Inactivated Bacillus subtilis Spores as a Heterologous Antibody Booster for COVID-19 Vaccines.

The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have threatened the world for more than 2 years. Multiple vaccine candidates have been developed and approved for emergency use by specific markets, but multiple doses are required to maintain the antibody level. Preliminary safety and immunogenicity data about an oral dose vaccine candidate using recombinant Bacillus subtilis in healthy adults were reported previously from an investigator-initiated trial in Hong Kong. Additional data are required in order to demonstrate the safety and efficacy of the candidate as a heterologous booster in vaccinated recipients. In an ongoing, placebo-controlled, observer-blinded, fixed dose, investigator-initiated trial conducted in the Macau, we randomly assigned healthy adults, 21 to 62 years of age to receive either placebo or a Bacillus subtilis oral dose vaccine candidate, which expressed the spike protein receptor binding domain of SARS-CoV-2 on the spore surface. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. For both the active vaccine and placebo, participants received three courses in three consecutive days. A total of 16 participants underwent randomization: 9 participants received vaccine and 7 received placebo. No observable local or systemic side-effect was reported. In both younger and older adults receiving placebo, the neutralizing antibody levels were gradually declining, whereas the participants receiving the antibody booster showed an increase in neutralizing antibody level.

Temporal Control of the WNT Signaling Pathway During Cardiac Differentiation Impacts Upon the Maturation State of Human Pluripotent Stem Cell Derived Cardiomyocytes.

Inefficient differentiation and insufficient maturation are barriers to the application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for research and therapy. Great strides have been made to the former, and multiple groups have reported cardiac differentiation protocol that can generate hPSC-CMs at high efficiency. Although many such protocols are based on the modulation of the WNT signaling pathway, they differ in their timing and in the WNT inhibitors used. Little is currently known about whether and how conditions of differentiation affect cardiac maturation. Here we adapted multiple cardiac differentiation protocols to improve cost-effectiveness and consistency, and compared the properties of the hPSC-CMs generated. Our results showed that the schedule of differentiation, but not the choice of WNT inhibitors, was a critical determinant not only of differentiation efficiency, which was expected, but also CM maturation. Among cultures with comparable purity, hPSC-CMs generated with different differentiation schedules vary in the expression of genes which are important for developmental maturation, and in their structural, metabolic, calcium transient and proliferative properties. In summary, we demonstrated that simple changes in the schedule of cardiac differentiation could promote maturation. To this end, we have optimized a cardiac differentiation protocol that can simultaneously achieve high differentiation efficiency and enhanced developmental maturation. Our findings would advance the production of hPSC-CMs for research and therapy.

Facteurs de risque d'éclosion de SRAS-CoV-2 dans les résidences pour aînés en Ontario, au Canada: étude de cohorte à l'échelle de la population.

CONTEXTE: L'épidémiologie de l'infection au SRAS-CoV-2 dans les résidences pour aînés (offrant une aide à la vie autonome), est pour une bonne part inconnue. Nous avons étudié le lien entre les caractéristiques des résidences et des communautés avoisinantes et le risque d'éclosion de SRAS-CoV-2 dans les résidences pour aînés depuis le début de la première vague de la pandémie de COVID-19. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective dans la population des résidences pour aînés certifiées en Ontario, au Canada, entre le 1er mars et le 18 décembre 2020. Notre paramètre principal était toute éclosion de SRAS-CoV-2 (≥ 1 cas confirmé parmi les résidents ou le personnel au moyen d'un test d'amplification des acides nucléiques). Nous avons utilisé la méthode des risques proportionnels avec prédicteurs chronologiques pour modéliser les liens entre les caractéristiques des résidences et des communautés avoisinantes et les éclosions de SRAS-CoV-2. RÉSULTATS: Notre cohorte a inclus l'ensemble des 770 résidences privées pour aînés (RPA) certifiées en Ontario qui hébergeaient 56 491 résidents. On a dénombré 273 (35,5 %) résidences pour aînés qui ont connu 1 éclosion de SRAS-CoV-2 ou plus; 1944 résidents (3,5 %) et 1101 employés (3,0 %) ont contracté l'infection. Ces cas étaient inégalement distribués entre les résidences. En effet, 2487 cas parmi les résidents et le personnel (81,7 %) sont survenus dans 77 résidences (10 %). Le rapport de risque ajusté d'une éclosion de SRAS-CoV-2 dans une résidence a été clairement associé aux établissements qui avaient une grande capacité d'accueil, qui comportaient des unités de soins de longue durée, qui appartenaient à de plus grandes bannières et offraient plusieurs services sur place, qui se trouvaient dans des régions marquées par une hausse de l'incidence régionale de SRAS-CoV-2 et où la concentration ethnique à l'échelle de la communauté était supérieure. INTERPRÉTATION: Certaines caractéristiques facilement identifiables des résidences pour aînés sont associées de manière indépendante aux éclosions de SRAS-CoV-2 et peuvent faciliter l'évaluation des risques et orienter la priorisation de la vaccination.

Risk factors for outbreaks of SARS-CoV-2 infection at retirement homes in Ontario, Canada: a population-level cohort study.

BACKGROUND: The epidemiology of SARS-CoV-2 infection in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between home-and community-level characteristics and the risk of outbreaks of SARS-CoV-2 infection in retirement homes since the beginning of the first wave of the COVID-19 pandemic. METHODS: We conducted a population-based, retrospective cohort study of licensed retirement homes in Ontario, Canada, from Mar. 1 to Dec. 18, 2020. Our primary outcome was an outbreak of SARS-CoV-2 infection (≥ 1 resident or staff case confirmed by validated nucleic acid amplification assay). We used time-dependent proportional hazards methods to model the associations between retirement home- and community-level characteristics and outbreaks of SARS-CoV-2 infection. RESULTS: Our cohort included all 770 licensed retirement homes in Ontario, which housed 56 491 residents. There were 273 (35.5%) retirement homes with 1 or more outbreaks of SARS-CoV-2 infection, involving 1944 (3.5%) residents and 1101 staff (3.0%). Cases of SARS-CoV-2 infection were distributed unevenly across retirement homes, with 2487 (81.7%) resident and staff cases occurring in 77 (10%) homes. The adjusted hazard of an outbreak of SARS-CoV-2 infection in a retirement home was positively associated with homes that had a large resident capacity, were co-located with a long-term care facility, were part of larger chains, offered many services onsite, saw increases in regional incidence of SARS-CoV-2 infection, and were located in a region with a higher community-level ethnic concentration. INTERPRETATION: Readily identifiable characteristics of retirement homes are independently associated with outbreaks of SARS-CoV-2 infection and can support risk identification and priority for vaccination.

Expression of SARS-CoV-2 Spike Protein Receptor Binding Domain on Recombinant B. subtilis on Spore Surface: A Potential COVID-19 Oral Vaccine Candidate.

Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have been developed to prevent SARS-CoV-2 infection. Although some of them have already been approved under the COVID-19 pandemic, various drawbacks, including severe side effects and the requirement for sub-zero temperature storage, may hinder their applications. Bacillus subtilis (B. subtilis) is generally recognized as a safe and endotoxin-free Gram-positive bacterium that has been extensively employed as a host for the expression of recombinant proteins. Its dormant spores are extraordinarily resistant to the harsh environment in the gastrointestinal tract. This feature makes it an ideal carrier for oral administration in resisting this acidic environment and for release in the intestine. In this study, an engineered B. subtilis spore expressing the SARS-CoV-2 spike protein receptor binding domain (sRBD) on the spore surface was developed. In a pilot test, no adverse health event was observed in either mice or healthy human volunteers after three oral courses of B. subtilis spores. Significant increases in neutralizing antibody against sRBD, in both mice and human volunteers, after oral administration were also found. These findings may enable the further clinical developments of B. subtilis spores as an oral vaccine candidate against COVID-19 in the future.