Heterologous prime-boost with mRNA-1273 stimulates persistent neutralising antibodies in BBIBP-CorV-vaccinated individuals.

BBIBP-CorV inactivated vaccine is one of the most prevalent vaccines globally, but immune responses are far less studied than novel COVID-19 vaccine platforms. Longitudinal studies on BBIBP-CorV with homologous and heterologous booster doses are limited. This study follows a subset of participants from a national study comparing the immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody (NAb). Homologous and heterologous booster dose significantly increased NAb levels in BBIBP-CorV-vaccinated individuals. Similar NAb levels were observed 1 month following BNT162b2 or mRNA-1273 booster. Interestingly, NAb persisted following mRNA-1273 booster (n = 95), but waned significantly at 6 and 9 months following BNT162b2 booster (n = 50; P > 0.001). The persistence of NAb was also observed following breakthrough infection. This study provides evidence that not all mRNA vaccines are equal in the longer term and should provide valuable information for policy makers planning booster programmes for BBIBP-CorV vaccinated populations.

Immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody in the Bruneian population: Protocol for a national longitudinal study.

INTRODUCTION: Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2-6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2). METHODS AND ANALYSIS: Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2-6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections. ETHICS AND DISSEMINATION: This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies.

Applications of next generation sequencing in the screening and diagnosis of thalassemia: A mini-review.

Thalassemias are a group of inherited blood disorders that affects 5-7% of the world population. Comprehensive screening strategies are essential for the management and prevention of this disorder. Today, many clinical and research laboratories have widely utilized next-generation sequencing (NGS) technologies to identify diseases, from germline and somatic disorders to infectious diseases. Yet, NGS application in thalassemia is limited and has just recently surfaced due to current demands in seeking alternative DNA screening tools that are more efficient, versatile, and cost-effective. This review aims to understand the several aspects of NGS technology, including its most current and expanding uses, advantages, and limitations, along with the issues and solutions related to its integration into routine screening and diagnosis of thalassemias. Hitherto, NGS has been a groundbreaking technology that offers tremendous improvements as a diagnostic tool for thalassemia in terms of its higher throughput, accuracy, and adaptability. The superiority of NGS in detecting rare variants, solving complex hematological problems, and providing non-invasive alternatives to neonatal diagnosis cannot be overlooked. However, several pitfalls still preclude its use as a stand-alone technique over conventional methods.

Technology-assisted adaptive recruitment strategy for a large nation-wide COVID-19 vaccine immunogenicity study in Brunei.

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods.

Thalassemia in Asia 2021 Thalassemia in Brunei Darussalam.

Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and control program to reduce its prevalence. In order to obtain reliable prevalence data, the gene frequencies of the thalassemias and other hemoglobinopathies should be investigated. Molecular studies on thalassemia have yet to be done for Brunei's population. It was estimated that carriers of thalassemia or hemoglobinopathies in Brunei is approximately 5.0% or less of the overall population. There are about 200 current cases of thalassemia and other hemoglobinopathies including adults and children reported across all four districts of Brunei. Blood parameter analysis, microscopy, hemoglobin (Hb) electrophoresis and high performance liquid chromatography (HPLC) are the most common methods of investigation in aiding diagnosis in the hospital laboratory. Genotyping analysis conducted in an overseas laboratory has been employed to confirm some diagnosis. Compiled data from 2009-2017 at the Hematology Laboratory of the Raja Isteri Pengiran Anak Saleha Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, Brunei Darussalam, showed that the most reported diagnoses are α-thalassemia (α-thal) trait, ß-thalassemia (ß-thal) trait, heterozygous Hb E (HBB: c.79G>A)/ß-thal, ß-thal major (ß-TM) and ß-thal intermedia (ß-TI). The data reported indicate the importance of establishing a thalassemia registry with relevant data on patients and patient outcomes as a tool for monitoring and improving patient care.

Herbal Plants: The Role of AhR in Mediating Immunomodulation.

The prevalence of chronic inflammatory diseases including inflammatory bowel disease (IBD), autoimmunity and cancer have increased in recent years. Herbal-based compounds such as flavonoids have been demonstrated to contribute to the modulation of these diseases although understanding their mechanism of action remains limited. Flavonoids are able to interact with cellular immune components in a distinct way and influence immune responses at a molecular level. In this mini review, we highlight recent progress in our understanding of the modulation of immune responses by the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor whose activity can be regulated by diverse molecules including flavonoids. We focus on the role of AhR in integrating signals from flavonoids to modulate inflammatory responses using in vitro and experimental animal models. We also summarize the limitations of these studies. Medicinal herbs have been widely used to treat inflammatory disorders and may offer a valuable therapeutic strategy to treat aberrant inflammatory responses by modulation of the AhR pathway.

Conducting multiple mini-interviews in the midst of COVID-19 pandemic.

Multiple mini-interview (MMI) is a 'multiple sample-based' approach comprising multiple focused encounters intended to access and assess a range of attributes in order to gain more objectively multiple impressions of an applicant's interpersonal skills, thoughtfulness and general demeanour. It is designed to focus on four domains that are not considered to be comprehensive, but are considered to be vital for a successful career in the health sciences: critical thinking, ethical decision making, communication and knowledge of the healthcare system. Traditionally, the MMI is conducted face-to-face, but with COVID-19 pandemic and the implementation of social distancing measures, no onsite or campus teaching, banning of mass gatherings and cancellation of face-to-face interviews, Pengiran Anak Puteri Rashidah Sa'adatul Bolkiah Institute of Health Sciences at Universiti Brunei Darussalam explored the feasibility of conducting MMI through virtual means. This report provides an account of our experience in conducting internet-MMI for the selection of new applicants into the August 2020 cohort of the Medicine programme. We also aimed to determine whether the scores derived from internet-MMI were reliable and equivalent to the scores derived from traditional MMI.

A deficiency in nucleoside salvage impairs murine lymphocyte development, homeostasis, and survival.

The homeostasis of the immune system is tightly controlled by both cell-extrinsic and -intrinsic mechanisms. These regulators, not all known to date, drive cells in and out of quiescence when and where required to allow the immune system to function. In this article, we describe a deficiency in deoxycytidine kinase (DCK), one of the major enzymes of the nucleoside salvage pathway, which affects peripheral T cell homeostatic proliferation and survival. As a result of an N-ethyl-N-nitrosourea-induced mutation in the last α helix of DCK, a functionally null protein has been generated in the mouse and affects the composition of the hematopoietic system. Both B and T lymphocyte development is impaired, leading to a state of chronic lymphopenia and to a significant increase in the number of myeloid cells and erythrocytes. In the periphery, we found that mutant lymphocytes adopt a CD44(high)CD62L(low) memory phenotype, with high levels of proliferation and apoptosis. These phenotypes are notably the result of a cell-extrinsic-driven lymphopenia-induced proliferation as wild-type cells transferred into DCK-deficient recipients adopt the same profile. In addition, DCK also regulates lymphocyte quiescence in a cell-intrinsic manner. These data establish dCK as a new regulator of hematopoietic integrity and lymphocyte quiescence and survival.