The effects of three different daily plant stanol ester intakes on influenza vaccination responses: a double-blind, randomized, placebo-controlled intervention study in older adults.

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesions.

Dietary plant stanol ester consumption improves immune function in asthma patients: results of a randomized, double-blind clinical trial

BackgroundThe reduced effectiveness of standard-dose influenza vaccines in persons ≥65 years of age led to the preferential recommendation to use high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) vaccines for this age group. Sleep is an important modulator of immune responses to vaccines and poor sleep health is common in older adults. However, potential effects of poor sleep health on immune responses to influenza vaccination in older adults remain largely unknown.MethodsWe conducted a cohort study of 210 healthy participants age ≥65 years, who received either seasonal high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) influenza vaccine. We assessed sleep characteristics in this cohort by standardized questionnaires and measured the antibody titer against influenza A/H3N2 virus in serum of study participants by hemagglutination inhibition assay on the day of immunization and 28 days thereafter. We then assessed the association between sleep characteristics and antibody titers.ResultsOur results demonstrated that male, but not female, study participants with excessive daytime sleepiness had an impaired influenza A/H3N2-specific antibody response at Day 28 post-vaccination. No other associations were found between antibody titer and other sleep characteristics, including sleep quality and obstructive sleep apnea.ConclusionOur results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults.

ABSTRACTBackground: The advantages of dual pneumococcal and influenza vaccination in older adults have not been clarified and controversy remains regarding their optimal use.Methods: This meta-analysis was conducted on 25 January 2018 using PubMed, the Cochrane Library, and Embase databases. Seventeen studies were selected ultimately for meta-analysis using a multi-step approach by two separate authors. Primary outcomes were pneumonia, pneumococcal pneumonia, influenza, hospitalization, and all-cause mortality rates, and the secondary outcome was adverse effects (AEs).Results: The additive preventive effects of dual influenza and pneumococcal vaccination versus influenza vaccination alone for pneumonia and death were 15% (95% confidence interval [CI]: 4-24%) and 19% (95% CI: 6-30%), respectively. Compared with pneumococcal vaccination alone, dual influenza and pneumococcal vaccination resulted in a 24% (95% CI: 16-31%) reduction in pneumonia and a 28% (95% CI: 13-40%) reduction in death. Compared with placebo or no vaccination, the effectiveness of dual vaccination was 29% (95% CI: 14-42%) for pneumonia, 38% (95% CI: 25-49%) for death, 35% (95% CI: 22-46%) for influenza, and 18% (95% CI: 6-29%) for hospitalization. Both vaccines showed acceptable safety profiles and AEs were mild or moderate.Conclusion: Our findings highlight the importance of concomitant influenza and pneumococcal vaccination in older adults.

Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known whether these polymorphisms are also associated with variations in serum plant sterol concentrations during interventions affecting plant sterol metabolism. We therefore decided to study changes in serum plant sterol concentrations with ABCG5/G8 polymorphisms after consumption of plant stanol esters, which decrease plasma plant sterol concentrations. Cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8 T400K genotype, as were changes in serum plant sterol concentrations after consumption of plant stanols. The reduction of -57.1 +/- 38.3 10(2) x micromol/mmol cholesterol for sitosterol in TT subjects was significantly greater compared with the -36.0 +/- 18.7 reduction in subjects with the TK genotype (P = 0.021) and the -16.9 +/- 13.0 reduction in subjects with the KK genotype (P = 0.047). Changes in serum campesterol concentrations showed a comparable association. No association with serum LDL cholesterol was found. Genetic variation in ABCG8 not only explains cross-sectional differences in serum plant sterol concentrations but also determines a subject's responsiveness to changes in serum plant sterols during interventions known to affect plant sterol metabolism.

Customary Use of Plant Sterol and Plant Stanol Enriched Margarine Is Associated with Changes in Serum Plant Sterol and Stanol Concentrations in Humans1

Background: previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens. The 2012-2013 northern hemisphere influenza season was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines. There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay. Methods: samples collected as part of a randomized controlled trial (NCT01427309) evaluating the efficacy of IIV-HD vs IIV-SD in adults ≥65 years were available for testing; one third of trial participants provided post-vaccination sera. This sub-study utilized a case-cohort design, in which 675 representative samples collected during the 2012-2013 season of the study (from individuals who either developed polymerase chain reaction/culture confirmed H3N2 influenza illness [N=123] or belonged to a random subset of 10% of non-cases [N=552]) were selected for expanded testing. Expanded immunogenicity was assessed with an HAI assay using an MDCK cell-propagated A/ Victoria/361 (H3N2) antigen, a viral neutralization assay (NT) using both eggand cell-propagated A/Victoria/361 (H3N2) antigens, and an enzyme-linked lectin assay (ELLA) for anti-neuraminidase (N2) antibodies. Geometric mean titers (GMT) were estimated for IIV-HD and IIV-SD recipients using weighted averages and were compared as GMT ratios (IIV-HD/IIV-SD). Results: samples from 318 IIV-HD and 357 IIV-SD recipients were assayed. The GMT ratios (and 95% Confidence Intervals) were 1.48 (1.26; 1.73), 1.53 (1.29; 1.82), 1.75 (1.43; 2.15), and 1.42 (1.23; 1.65) for cell-propagated HAI, egg-propagated NT, cell-propagated NT, and N2-ELLA, respectively. The GMT ratio for the full immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients) assessed by HAI assay using egg-propagated A/Victoria/361 was 1.82 (1.71; 1.94). Conclusion: IIV-HD is associated with significantly improved immunogenicity compared to IIV-SD in older adults as assessed using a range of different assays. BACKGROUND • Adults ≥65 years of age are particularly vulnerable to influenza-associated complications, accounting for most seasonal influenza-related hospitalizations and deaths1,2 • The high burden of influenza in this population persists despite documented improvements in vaccination rates3 • An unmet medical need is therefore recognized for improved influenza vaccines in adults 65 years of age and older4,5 • Previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens6,7,8 • A recently completed randomized, controlled efficacy study demonstrated that IIV-HD was 24.2% (95% confidence interval [CI], 9.7%–36.5%) more efficacious than a IIV-SD in preventing laboratory-confirmed symptomatic influenza in adults 65 years of age and older9 • The second year of the efficacy study (2012-2013 northern hemisphere influenza season) was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines such as the ones used in the study. In contrast, cell-propagated vaccine antigens were considered well-matched to circulating H3N2 viruses10,11 • Consistent with previous studies, the immunogenicity of IIV-HD was significantly improved compared to IIV-SD as determined by the standard HAI assay using egg-propagated vaccine antigens in the full Year 2 immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients), with a corresponding GMT ratio of 1.82 (95% CI 1.71; 1.94)9 Figure 1. HAI (Egg-propagated) G M T 0 100 200 300 400 500 600 IIV-HD IIV-SD IIV: inactivated influenza vaccine; HD: high-dose; SD: standard-dose GMT: Geometric Mean Titers; HAI: Hemagglutination inhibition; Error bars represent 95% confidence intervals • There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay.12 OBJECTIVES • To compare the immunogenicity of IIV-HD vs IIV-SD in adults ≥65 years of age against the A/Victoria/361/2011 (H3N2) influenza virus using methods other than the HAI assay based on egg-propagated antigens.

Comparison of the safety and immunogenicity of a novel Matrix-M-adjuvanted nanoparticle influenza vaccine with a quadrivalent seasonal influenza vaccine in older adults: a phase 3 randomised controlled trial

Cross-protective potential of a MF59-adjuvanted quadrivalent influenza vaccine in older adults

Effects of plant sterol- or stanol-enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects

BackgroundVaccination is important in influenza prevention but the immune response wanes with age. The circadian nature of the immune system suggests that adjusting the time of vaccination may provide an opportunity to improve immunogenicity. Our previous cluster trial in Birmingham suggested differences between morning and afternoon vaccination for some strains in the influenza vaccine in older adults. Whether this effect is also seen in a younger age group with less likelihood of compromised immunity is unknown. We therefore conducted an individual-based randomized controlled trial in Guangzhou to test the hypothesis that influenza vaccination in the morning induces a stronger immune response in older adults than afternoon vaccination. We included adults in middle age to determine if the effect was also seen in younger age groups.ResultsOf the 418 participants randomised, 389 (93.1%, 191 middle-aged adults aged 50–60 years and 198 older adults aged 65–75 years) were followed up. Overall, there was no significant difference between the antibody titers (geometric mean /95% CI) after morning vs afternoon vaccination (A/H1N1: 39.9 (32.4, 49.1) vs. 33.0 (26.7, 40.7), p = 0.178; A/H3N2: 92.2 (82.8, 102.7) vs. 82.0 (73.8, 91.2), p = 0.091; B: 15.8 (13.9, 17.9) vs. 14.4 (12.8, 16.3), p = 0.092), respectively. However, in pre-specified subgroup analyses, post-vaccination titers for morning versus afternoon vaccination in the 65–75 years subgroup were (A/H1N1): 49.5 (36.7, 66.6) vs. 32.9 (24.7, 43.9), p = 0.050; (A/H3N2): 93.5 (80.6, 108.5) vs. 73.1 (62.9, 84.9), p = 0.021; (B): 16.6 (13.8, 20.1) vs. 14.4 (12.3, 17.0), p = 0.095, respectively. Among females, antibody titers for morning versus afternoon vaccination were (A/H1N1): 46.9 (35.6, 61.8) vs. 31.1 (23.8, 40.7), p = 0.030; (A/H3N2): 96.0 (83.5, 110.3) vs. 84.7 (74.4, 96.5), p = 0.176; (B): 14.8 (12.7, 17.3) vs. 13.0 (11.3, 14.9), p = 0.061, respectively. In the 50–60 years old subgroup and males, there were no significant differences between morning and afternoon vaccination.ConclusionsMorning vaccination may enhance the immunogenicity to influenza vaccine in adults aged over 65 and women. An intervention to modify vaccination programs to vaccinate older individuals in the morning is simple, cost free and feasible in most health systems.

Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study

Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults

Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.

Annual influenza vaccination is important for older adults to prevent morbidity and mortality from seasonal influenza. Although the United States has had limited success in increasing influenza vaccination, the rise of the COVID-19 pandemic in 2020 may have changed older adults’ approach to vaccination. The objective of this study is to determine factors associated with influenza vaccination in 2019 and 2020 and compare their degree of associations across the two years. Data from the 2019 and 2020 National Health Interview Survey, a nationally representative cross-sectional interview, were collected for variables relating to annual influenza vaccination and possible associated factors. Data were analyzed using chi-square tests and multiple logistic regression. The results show that never having received a vaccination for pneumonia increased the odds of receiving an influenza vaccination by 6.79–7.80 times. Recent specialist care for eye or oral health significantly increased the odds of receiving an influenza vaccination. Being a smoker, identifying as African American, and considering oneself to have excellent overall health were associated with significantly lower odds of receiving a vaccination. Although self-reported feelings of anxiety were not associated with vaccination in 2019, they increased the odds in 2020. Overall, influenza vaccination in older adults may be tied to reliable healthcare access and perceived susceptibility to infectious respiratory diseases.