Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice.

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)-for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development. We found that all four of the adjuvant candidates surpassed alum with respect to their capacity to induce enhanced and durable antigen-specific antibody responses. The TLR-agonist-based adjuvants CpG1018 (TLR9) and AS37 (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, and AS03 induced a balanced Th1/Th2 response. Consistent with this, adjuvants induced distinct patterns of early innate responses. Finally, vaccines adjuvanted with AS03, AS37, and CpG1018/alum-induced durable neutralizing-antibody responses and significant protection against the B.1.351 variant 7 months following immunization. These results, together with our recent results from an identical study in non-human primates (NHPs), provide a comparative benchmarking of five clinically relevant vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV-2 subunit vaccines to provide durable protection against the B.1.351 variant. Furthermore, these results reveal differences between the widely-used C57BL/6 mouse strain and NHP animal models, highlighting the importance of species selection for future vaccine and adjuvant studies.

Impact of vitamin D deficiency on COVID-19.

BACKGROUND & AIMS: COVID-19 has emerged as a global pandemic affecting millions of people. Vitamin D deficiency is one of the risk factors for increased susceptibility to COVID-19. This study aimed to examine the correlation between the prevalence of vitamin D deficiency and COVID-19 infection and mortality rates among the adult population in European and Asian continents. METHODS: Prevalence of vitamin D deficiency in each country was retrieved through literature searching on PubMed® database for the last ten years. As of December, 31st 2020, COVID-19 infections and mortalities per million population were extracted from the 'real time' statistics of the Worldometer website. The association between both vitamin D deficiency and COVID-19 infections and mortalities were explored. RESULTS: Forty seven countries were included in the analysis. The prevalence of vitamin D deficiency ranged from 6.9 to 81.8% in European countries and 2.0-87.5% in Asian countries. Significantly positive correlations were observed for both COVID-19 infection (r = 0.76; p < 0.001) and mortality rates (r = 0.75; p < 0.001) in the Asian continent. The correlation values for the infections and mortality rates in the European continent were (r = 0.37; p = 0.08) and (r = 0.43; p = 0.04) respectively. When both the continents were combined, the correlation results for both infection (r = 0.42; p = 0.003) and mortality (r = 0.35; p = 0.016) rates with vitamin D deficiency values remained significant. CONCLUSION: Prevalence of vitamin D deficiency was significantly associated with the mortality rate of COVID-19 in Europe and Asia. The association between the infection rate and prevalence of vitamin D deficiency was significant for Asia only. Both the associations were significant when the two continents were combined in the analysis. Therefore we suggest that vitamin D supplementation could play a key role in the prevention and/or treatment of the COVID-19 patients.

Assessment of Motivational Cognitions in Diabetes Self-Care: the Motivation Thought Frequency Scales for Glucose Testing, Physical Activity and Healthy Eating.

PURPOSE: There is a need for improved measurement of motivation for diabetes self-care. The Elaborated Intrusion Theory of Desire offers a coherent framework for understanding and identifying the cognitive-affective events that constitute the subjective experience of motivation and may therefore inform the development of such an instrument. Recent research has shown the resultant Motivation Thought Frequency scale (MTF) to have a stable factor structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) when applied to physical activity, excessive snacking or alcohol use in the general population. The current study aimed to confirm the four-factor structure of the MTF for glucose testing, physical activity and healthy eating in people with type 2 diabetes. Associations with self-reports of concurrent diabetic self-care behaviours were also examined. METHOD: Confirmatory factor analyses tested the internal structure, and multiple regressions assessed the scale's relationship with concurrent self-care behaviours. The MTF was completed by 340 adults with type 2 diabetes, and 237 from that sample also reported self-care behaviours. Separate MTFs assessed motivation for glucose testing, physical activity and healthy eating. Self-care was assessed using questions from the Summary of Diabetes Self-Care Activities. RESULTS: The MTF for each goal achieved an acceptable fit on all indices after selected errors within factors were allowed to intercorrelate. Intensity and Self-Efficacy Imagery provided the strongest and most consistent correlations with relevant self-care behaviours. CONCLUSION: Results provide preliminary support for the MTF in a diabetes sample. Testing of its sensitivity to change and its predictive utility over time is needed.

Increasing Protein Distribution Has No Effect on Changes in Lean Mass During a Rugby Preseason.

Increasing the frequency of protein consumption is recommended to stimulate muscle hypertrophy with resistance exercise. This study manipulated dietary protein distribution to assess the effect on gains in lean mass during a rugby preseason. Twenty-four developing elite rugby athletes (age 20.1 ± 1.4 years, mass 101.6 ± 12.0 kg; M ± SD) were instructed to consume high biological value (HBV) protein at their main meals and immediately after resistance exercise while limiting protein intake between meals. To manipulate protein intake frequency, the athletes consumed 3 HBV liquid protein supplements (22 g protein) either with main meals (bolus condition) or between meals (frequent condition) for 6 weeks in a 2 × 2 crossover design. Dietary intake and change in lean mass values were compared between conditions by analysis of covariance and correlational analysis. The dietary manipulation successfully altered the protein distribution score (average number of eating occasions containing > 20 g of protein) to 4.0 ± 0.8 and 5.9 ± 0.7 (p < .01) for the bolus and frequent conditions, respectively. There was no difference in gains in lean mass between the bolus (1.4 ± 1.5 kg) and frequent (1.5 ± 1.4 kg) conditions (p = .91). There was no clear effect of increasing protein distribution from approximately 4-6 eating occasions on changes in lean mass during a rugby preseason. However, other dietary factors may have augmented adaptation.

The effect of a whey protein supplement dose on satiety and food intake in resistance training athletes.

OBJECTIVE: Many athletes perform resistance training and consume dietary protein as a strategy to promote anabolic adaptation. Due to its high satiety value, the regular addition of supplemented dietary protein could plausibly displace other key macronutrients such as carbohydrate in an athlete's diet. This effect will be influenced by the form and dose of protein. Therefore, this study assessed the impact of liquid whey protein dose manipulation on subjective sensations of appetite and food intake in a cohort of athletes. DESIGN: Ten male athletes who performed both resistance and aerobic (endurance) training (21.2 ± 2.3 years; 181.7 ± 5.7 cm and 80.8 ± 6.1 kg) were recruited. In four counter-balanced testing sessions they consumed a manipulated whey protein supplement (20, 40, 60 or 80 g protein) 1 hour after a standardised breakfast. Subsequent energy intake was measured 3 hours after the protein supplement using an ad libitum test meal. Subjective appetite sensations were measured periodically during the test day using visual analogue scales. RESULTS: All conditions resulted in a significant decrease in ratings of hunger (50-65%; P < 0.05) at the time of supplement consumption. However, there were no significant differences between the conditions at any time point for subjective appetite sensations or for energy consumed in the ad libitum meal: 4382 ± 1004, 4643 ± 982, 4514 ± 1112, 4177 ± 1494 kJ respectively. CONCLUSION: Increasing whey protein supplement dose above 20 g did not result in a measurable increase in satiety or decrease in food intake. However, the inclusion of additional whey protein supplementation where not otherwise consumed could plausibly reduce dietary intake.

The Measurement and Interpretation of Dietary Protein Distribution During a Rugby Preseason.

Evidence suggests that increasing protein distribution may be desirable to promote muscle protein synthesis (MPS) in combination with resistance exercise. However, there is a threshold above which additional protein consumption has limited benefit for MPS and may promote protein loss due to increased oxidation. This study aimed to measure daily protein intake and protein distribution in a cohort of rugby players. Twenty-five developing elite rugby union athletes (20.5 ± 2.3 years, 100.2 ± 13.3 kg, 184.4 ± 7.4 cm) were assessed at the start and end of a rugby preseason. Using a 7-day food diary the reported daily protein intake was 2.2 ± 0.7 g · kg · day(-1) which exceeds daily recommendations. The reported carbohydrate intake was 3.6 ± 1.3 g · kg · day(-1) which may reflect a suboptimal intake or dietary underreporting. In general, the rugby athletes were regularly consuming more than 20 g of protein; 3.8 ± 0.9 times per day (68 ± 18% of eating occasions). In addition to documenting current dietary intakes, an excess protein estimation score was calculated to determine how frequently the rugby athletes consumed protein above a known effective dose with a margin of error. 2.0 ± 0.9 eating occasions contained protein in excess of doses (20 g) known to promote MPS. Therefore, it is currently unclear whether the consumption of regular large doses of protein will benefit rugby athletes via increasing protein distribution, or whether high protein intakes may have unintended effects including a reduction in carbohydrate and/or energy intake.

Coffee for morning hunger pangs. An examination of coffee and caffeine on appetite, gastric emptying, and energy intake.

Coffee is one of the most widely consumed beverages in the world and has a number of potential health benefits. Coffee may influence energy expenditure and energy intake, which in turn may affect body weight. However, the influence of coffee and its constituents - particularly caffeine - on appetite remains largely unexplored. The objective of this study was to examine the impact of coffee consumption (with and without caffeine) on appetite sensations, energy intake, gastric emptying, and plasma glucose between breakfast and lunch meals. In a double-blind, randomised crossover design. Participants (n = 12, 9 women; Mean ± SD age and BMI: 26.3 ± 6.3 y and 22.7 ± 2.2 kg•m⁻²) completed 4 trials: placebo (PLA), decaffeinated coffee (DECAF), caffeine (CAF), and caffeine with decaffeinated coffee (COF). Participants were given a standardised breakfast labelled with ¹³C-octanoic acid and 225 mL of treatment beverage and a capsule containing either caffeine or placebo. Two hours later, another 225 mL of the treatment beverage and capsule was administered. Four and a half hours after breakfast, participants were given access to an ad libitum meal for determination of energy intake. Between meals, participants provided exhaled breath samples for determination of gastric emptying; venous blood and appetite sensations. Energy intake was not significantly different between the trials (Means ± SD, p> 0.05; Placebo: 2118 ± 663 kJ; Decaf: 2128 ± 739 kJ; Caffeine: 2287 ± 649 kJ; Coffee: 2016 ± 750 kJ); Other than main effects of time (p <0.05), no significant differences were detected for appetite sensations or plasma glucose between treatments (p > 0.05). Gastric emptying was not significantly different across trials (p > 0.05). No significant effects of decaffeinated coffee, caffeine or their combination were detected. However, the consumption of caffeine and/or coffee for regulation of energy balance over longer periods of time warrant further investigation.

Adherence to fish oil intervention in patients with chronic kidney disease.

OBJECTIVE: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. DESIGN: This was a nonrandomized intervention study. SETTING: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. PATIENTS: The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent. INTERVENTION: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report. RESULTS: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients. CONCLUSIONS: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.

Effects of an acute alpha-lactalbumin manipulation on mood and food hedonics in high- and low-trait anxiety individuals.

Serotonergic hypofunction is associated with a depressive mood state, an increased drive to eat and preference for sweet (SW) foods. High-trait anxiety individuals are characterised by a functional shortage of serotonin during stress, which in turn increases their susceptibility to experience a negative mood and an increased drive for SW foods. The present study examined whether an acute dietary manipulation, intended to increase circulating serotonin levels, alleviated the detrimental effects of a stress-inducing task on subjective appetite and mood sensations, and preference for SW foods in high-trait anxiety individuals. Thirteen high- (eleven females and two males; anxiety scores 45.5 (sd 5.9); BMI 22.9 (sd 3.0)kg/m(2)) and twelve low- (ten females and two males; anxiety scores 30.4 (sd 4.8); BMI 23.4 (sd 2.5) kg/m(2)) trait anxiety individuals participated in a placebo-controlled, two-way crossover design. Participants were provided with 40 g alpha-lactalbumin (LAC; l-tryptophan (Trp):large neutral amino acids (LNAA) ratio of 7.6) and 40 g casein (placebo) (Trp:LNAA ratio of 4.0) in the form of a snack and lunch on two test days. On both the test days, participants completed a stress-inducing task 2 h after the lunch. Mood and appetite were assessed using visual analogue scales. Changes in food hedonics for different taste and nutrient combinations were assessed using a computer task. The results demonstrated that the LAC manipulation did not exert any immediate effects on mood or appetite. However, LAC did have an effect on food hedonics in individuals with high-trait anxiety after acute stress. These individuals expressed a lower liking (P = 0.012) and SW food preference (P = 0.014) after the stressful task when supplemented with LAC.

Zinc supplementation at conventional doses does not improve the disturbance of taste perception in hemodialysis patients.

OBJECTIVE: To determine the effect of zinc supplementation on taste perception in a group of hemodialysis patients. DESIGN AND SETTING: Double-blind randomized placebo-controlled study in a teaching hospital dialysis unit. PATIENTS: Fifteen stable hemodialysis patients randomized to placebo (6 male, 2 female; median age, 67; range, 30 to 72 years) or treatment (5 male, 2 female; median age, 60; range, 31 to 76 years). INTERVENTION: Treatment group received zinc sulfate 220 mg per day for 6 weeks, and the placebo group received an apparently identical dummy pill. MAIN OUTCOME MEASURES: Taste scores by visual analogue scales, normalized protein catabolic rate and plasma, whole blood and red cell zinc levels. RESULTS: At baseline, sweet and salt tastes were identified correctly by both groups. Sour was often confused with salt. Sour solutions of different concentrations were not distinguishable. Taste scores were not different after 6 weeks for either group. There was no significant increment in zinc levels or normalized protein catabolic rate for either group. CONCLUSION: We found a disturbance of taste perception in hemodialysis patients, particularly for the sour modality, which was not corrected by this regimen of zinc supplementation. These results cast doubts on the conclusions of earlier studies that indicated an improvement in taste after zinc supplementation.