Advances in vaccinia virus-based vaccine vectors,with applications in flavivirus vaccine development

Historically, virulent variola virus infection caused hundreds of millions of deaths. The smallpox pandemic in human beings has spread for centuries until the advent of the attenuated vaccinia virus (VV) vaccine, which played a crucial role in eradicating the deadly contagious disease. Decades of exploration and utilization have validated the attenuated VV as a promising vaccine vehicle against various lethal viruses. In this review, we focus on the advances in VV-based vaccine vector studies, including construction approaches of recombinant VV, the impact of VV-specific pre-existing immunity on subsequent VV-based vaccines, and antigen-specific immune responses. More specifically, the recombinant VV-based flaviviruses are intensively discussed. Based on the publication data, this review aims to provide valuable insights and guidance for future VV-based vaccine development.     

Policy Analysis for Prevention and Control of Influenza in Aged Care

ObjectiveThis study aimed to analyze national influenza infection control policy documents within aged care settings by identifying the consistencies, inconsistencies, and gaps with the current evidence and by evaluating methodological quality. Aged care providers can use these findings to identify their policy documents' strengths and weaknesses.DesignA quality and content analysis of national level policy documents.Setting and ParticipantsAged care settings rely on national agencies' policy recommendations to control and prevent outbreaks. There is limited research on the effectiveness of control measures to prevent and treat influenza within aged care settings. Because of the complexities around aged care governance, the primary responsibility in developing a comprehensive facility-level, infection-prevention policy, falls to the providers.MethodsThe analysis was conducted using the (1) International Appraisal of Guidelines, Research and Evaluation assessment tool, containing 23 items across 6 domains; and the (2) Influenza Related Control Measures in Aged Care settings checklist, developed by the authors, with 82 recommendations covering: medical interventions, nonmedical interventions, and physical layout.ResultsThere were 19 documents from 9 different high-income countries, with a moderately high methodological quality in general. The quality assessment's average score was 40.2% (95% CI 31.9%–44.7%). “Stakeholder involvement” ranked third, and “Editorial independence” and “Rigor of development” had the lowest average scores across all domains. The content analysis' average score was 37.2% (95% CI 10.5%–21.5%). The highest scoring document (59.1%) included term definitions, cited evidence for recommendations, and clear measurable instructions. “Physical Layout” had the least coverage and averaged 21.9% (95% CI 4.2%–37.5%), which shows a substantial gap in built environment recommendations.Conclusions and ImplicationsExisting policy documents vary in their comprehensiveness. The higher scoring documents provide an ideal model for providers. The checklist tools can be used to assess and enhance documents. Further research on document end-user evaluation would be useful, as there is room for improvement in methodological quality and coverage of recommendation coverage, especially related to physical layout.     

Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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Prevalence of EBV infection in 1157 diseased cohorts in Nigeria: A systematic review and meta-analysis

BackgroundEpstein-Barr virus (EBV) is a member of the herpesvirus family that is known to ubiquitously infect people worldwide. However, the actual prevalence of EBV infection in diseased patients in Nigeria, remains unknown. This study was thus conducted to ascertain the true prevalence.MethodsA systematic review and meta-analysis of published data was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched for studies reporting the occurrence of EBV infection among patients with established diseases. Studies were included if they assessed EBV infection in diseased patients in Nigeria. Data were extracted and subsequently analysed using R software. Funnel plot and Egger's regression test was used to assess publication bias, while JBI prevalence tool was used to assess study quality.ResultsA total of 13 studies covering 228 cases of EBV infection among 1157 diseased patients were included. Summary estimates were computed using random-effects model. The pooled prevalence of EBV infection was 20.3% (95% CI: 10.8–34.9, I² ?= ?92.26, p ?< ?0.001). When stratified according to the type of disease, higher estimates were obtained for patients suffering from Kaposi's sarcoma (98.7%, 95% CI: 82.2–99.9) and Nasopharyngeal malignancy (85.7%, 95% CI: 70.0–93.9). A prevalence of 13.4% (95% CI: 6.0–27.4) and 12.2% (95% CI: 4.8–27.8) was derived for the most reported patient populations, lymphoma and HIV, respectively.ConclusionThis first meta-analysis on the prevalence of EBV among Nigerian patients suffering from various diseases reveals a prevalence that emphasises the need to routinely monitor EBV infection in all EBV-associated diseases in Nigeria.     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance

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Impact of Adding Oseltamivir to Usual Care on Quality-Adjusted Life-Years During Influenza-Like Illness

ObjectivesThe ALIC⁴E trial has shown that oseltamivir reduces recovery time while increasing the risk of nausea. This secondary analysis of the ALIC⁴E trial aimed to determine the gain in quality-adjusted life-years (QALYs) associated with adding oseltamivir to usual primary care in patients presenting with influenza-like illness (ILI).MethodsPatients with ILI were recruited during the influenza season (2015-2018) in 15 European countries. Patients were assigned to usual care with or without oseltamivir through stratified randomization (age, severity, comorbidities, and symptom onset). Patients’ health status was valued with the EQ-5D and visual analog scale (VAS) for up to 28 days. Average EQ-5D and VAS scores over time were estimated for both treatment groups using one-inflated beta regression in children (<13 years old) and adults (≥13 years old). QALY gain was calculated as the difference between the groups. Sensitivity analysis considered the value set to convert EQ-5D answers to summary scores and the follow-up period.ResultsIn adults, oseltamivir gained 0.0006 (95% confidence interval 0.0002-0.0010) QALYs, whereas no statistically significant gain was found in children (14-day follow-up, EQ-5D). QALY gains were statistically significant in patients aged ≥65 years, patients without relevant comorbidities, or patients experiencing symptoms for ≤48 hours. Using VAS and accounting for 28-day follow-up resulted in higher QALY gain.ConclusionsQALY gain owing to oseltamivir is limited compared with other diseases, and its clinical meaningfulness remains to be determined. Further analysis is needed to evaluate whether QALY gain and its impact on ILI treatment cost render oseltamivir cost-effective.     

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study

BackgroundDuring the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands.MethodsWe estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence.ResultsWith a decrease in numbers of sex partners of 15–25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred.ConclusionsDespite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.     

Maternal influenza vaccination and child mortality: Longitudinal,population-based linked cohort study

Influenza vaccination is recommended to protect mothers and their infants from influenza. Few studies have evaluated the association between maternal influenza vaccination and child mortality. We aimed to evaluate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and mortality among young children. This longitudinal, population-based cohort study included 191,247 maternal-child pairs in Western Australia between April 2012 and December 2017. Maternal vaccine information was obtained from a state-wide antenatal vaccination database. Mortality was defined as a record of a death registration. We used Cox proportional hazard models, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio of child mortality associated with in utero exposure to seasonal IIV. This study found no association between in utero exposure to seasonal IIV and mortality through age five years.