A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Surge Capacity Associated with Restrictions on Nonurgent Hospital Utilization and Expected Admissions during an Influenza Pandemic: Lessons from the Toronto Severe Acute Respiratory Syndrome Outbreak

Background Current influenza pandemic models predict a surge in influenza‐related hospitalizations in affected jurisdictions. One proposed strategy to increase hospital surge capacity is to restrict elective hospitalizations, yet the degree to which this measure would meet the anticipated is unknown. Objectives To compare the reduction in hospitalizations resulting from widespread nonurgent hospital admission restrictions during the Toronto severe acute respiratory syndrome (SARS) outbreak with the expected increase in admissions resulting from an influenza pandemic in Toronto. Methods The authors compared the expected influenza‐related hospitalizations in the first eight weeks of a mild, moderate, or severe pandemic with the actual reduction in the number of hospital admissions in Toronto, Ontario, during the first eight weeks of the SARS‐related restrictions. Results Influenza modeling for Toronto predicts that there will be 4,819, 8,032, or 11,245 influenza‐related admissions in the first eight weeks of a mild, moderate, or severe pandemic, respectively. In the first eight weeks of SARS‐related hospital admission restrictions, there were 3,654 fewer hospitalizations than expected in Toronto, representing a modest 12% decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000 population). Therefore, influenza‐related admissions could exceed the reduction in admissions resulting from restricted hospital utilization by 1,165 to 7,591 patient admissions, depending on pandemic severity, which corresponds to an excess of 0.44 to 2.91 influenza‐related admissions per 1,000 population per eight weeks, and an increase of 4% to 25% in the overall number of admissions, when compared with nonpandemic conditions. Conclusions Pandemic modeling for Toronto suggests that influenza‐related admissions would exceed the reduction in hospitalizations seen during SARS‐related nonurgent hospital admission restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic will likely require the implementation of other measures, including possibly stricter implementation of hospital utilization restrictions.     

Impact of anxiety,stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency

Background

Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).

Methods

This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.

Results

139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0–45) and 6 (min-max: 0–10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).

Conclusions

This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

     

The Effects of Sleep Quality and Resilience on Perceived Stress,Dietary Behaviors,and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia,Europe, and North America during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. Methods: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. Results: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. Conclusion: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.     

Vitamin D Status in Adolescents during COVID-19 Pandemic: A Cross-Sectional Comparative Study

Vitamin D has been claimed to be effective in the response to infections, including the respiratory syndrome coronavirus 2 (SARS-CoV-2). It is supposed that lockdown measures and fear of SARS-CoV-2 infection might reduce vitamin D levels through the modification of lifestyle. However, very few data exist on the association between lockdown measures and vitamin D status in humans. For this cross-sectional comparative study, adolescents (n = 298) aged 18 to 19 years were enrolled during the compulsory military fitness-for-duty evaluation between July and December 2020 in Southern Switzerland. Beyond anthropometric measurements, participants filled in a structured questionnaire about their lifestyle and a blood specimen was sampled for the determination of total 25-hydroxy-vitamin D. The obtained data were compared with those of 437 adolescents enrolled at the military fitness-for-duty evaluation during the same period of the year in the context of the CENERI study (2014–2016). The anthropometric measures were similar between the two study groups. The levels of vitamin D were also comparable (77 (64–91) vs. 74 (60–92) nmol/L, p = 0.50; median and interquartile range). A total of 38 (13%) and 43 (9.8%) subjects presented insufficient (<50 nmol/L) levels of vitamin D (p = 0.42) during the current pandemic and in the CENERI study, respectively. These data do not support the hypothesis that during the SARS-CoV-2 pandemic, late adolescents are at higher risk of vitamin insufficiency.     

The Perceived Impact of COVID-19 on Comfort Food Consumption over Time: The Mediational Role of Emotional Distress

The COVID-19 pandemic has had a significant impact on populations at an economic, health, and on an interpersonal level, it is still unclear how it has affected health-risk behaviors, such as comfort food consumption over time. This study longitudinally examines the effect of the perceived impact of COVID-19 on comfort food consumption and whether this effect is mediated by emotional distress. A convenience sample of 1048 students and university staff (academic and non-academic) from two universities completed monthly online surveys during the COVID-19 pandemic across six waves (W; W1 to W6). Participants reported their perceived impact of COVID-19 (economic, interpersonal, and health), comfort food consumption, and emotional distress (DASS-21). Using structural equation models, we found an indirect longitudinal effect of the perceived impact of COVID-19 (W1) on comfort food consumption (W3 to W6) through increased emotional distress (W2). The perceived negative impact of COVID-19 on comfort food consumption was fully mediated by the emotional distress during the first waves (W3 and W4), ending in a partial mediation in the last waves (W5 and W6). These findings contribute to disentangling the mechanisms by which the perceived impact of COVID-19 affects comfort food consumption over time, and highlight the role of emotional distress. Future interventions should address comfort food consumption by focusing on handling emotional distress during a crisis.