Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques

ABSTRACT Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut

Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques

IntroductionIt is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques.MethodsWe analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids.ResultsComposition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella-related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG.DiscussionOur findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota–vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life

Apolipoprotein C3 Polymorphisms, Cognitive Function and Diabetes in Caribbean Origin Hispanics

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74) living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted

Accepting the Internet-of-Things in our homes: The role of user skills

The present study investigates whether skills associated with operating the Internet-of-Things (IoT) contribute to the acceptance and (intended) usage of IoT technology and investigates to what extent these IoT skills are influenced by Internet skills. Extending the technology acceptance model (TAM), we conducted an online survey among 1356 respondents, a sample representative of the Dutch population. The results revealed that IoT skills directly contribute to IoT use and testify to the relevance of the TAM for predicting IoT acceptance and usage. However, people’s attitudes towards the IoT did not influence its acceptance, suggesting that users are not yet fully aware of how IoT use affects their privacy and quality of life in general. Furthermore, the results revealed that several Internet skills are an important precedent for IoT acceptance and usage. Mobile, information navigation, social, and creative Internet skills directly or indirectly contributed to the level of IoT skills. It can be concluded that people’s assessments of their IoT skills and that pragmatic considerations are important for its acceptance and that being skilled in using the IoT requires sufficient Internet skills

Relationship between muscle strength and dyslipidemia, serum 25(OH)D, and weight status among diverse schoolchildren: a cross-sectional analysis

Abstract Background The relationship between muscle strength and cardiometabolic risk factors in youth, and the potential influence of vitamin D status on this relationship, is not well understood. This study examined associations between muscle strength and dyslipidemia, serum 25-hydroxyvitamin D [25(OH)D], and weight status in diverse schoolchildren. Methods Measures of hand-grip strength (standardized for sex and body weight), anthropometrics (height and weight converted to BMI z-score [BMIz]), sociodemographics, and fasting blood concentrations of plasma HDL-C and triglycerides and serum 25(OH)D were collected from 350 4th-8th grade schoolchildren (11.2 ± 1.3 y, 49.4% female, 56.3% non-white/Caucasian). Logistic regression was used to measure associations between standardized tertiles of grip strength and blood lipids, 25(OH)D, and weight status along with associations between 25(OH)D and dyslipidemia and weight status. Results Children with higher grip strength had lower odds of overweight/obesity (OR: 0.03, 95% CI: 0.01-0.06, in the highest tertile of grip strength vs. lowest, p for trend< 0.0001), borderline/low HDL-C (OR: 0.28, 95% CI: 0.16-0.50, p for trend< 0.0001), and borderline/high triglycerides (OR: 0.48, 95% CI: 0.25-0.92, p for trend< 0.05), adjusting for covariates. Associations between blood lipids and grip strength became non-significant after further adjustment for BMIz. No association was observed between grip strength and 25(OH)D, nor between 25(OH)D and borderline/low HDL-C or weight status; however, vitamin D sufficiency was associated with lower odds of borderline/high triglycerides compared with vitamin D deficiency (OR: 0.26, 95% CI: 0.09-0.74, p for trend< 0.05) before BMIz adjustment. Conclusion Among racially/ethnically diverse children, muscle strength was associated with lower dyslipidemia. Longitudinal studies are needed to explore whether changes in muscle strength impact this relationship in children, independent of weight status. Trial registration This study was registered at www.clinicaltrials.gov (No. NCT01537809) on February 17, 2012

Integrating SDG 12 into Business Studies through Intercultural Virtual Collaboration

Intercultural Virtual Collaboration (IVC) has been a growing field in recent decades as it allows students from different cultures to work together without having to move physically. Besides providing students with an authentic experience that they are going to encounter in their future professional careers in increasingly globalised and digitised workplaces, more recently, IVC has also been used as a means to engage university students from different cultures in social and political issues that are common across societies. In this paper, we present an analysis of an IVC project that involved undergraduate Business students from a university in Spain and a university in the Netherlands where students from both universities were asked to collaborate online to develop a business case to analyse how companies communicate about the way they integrate SDGs in the different cultures involved. A content analysis of group reports delivered by students was carried out. In addition, intercultural competence development was measured through a questionnaire. Results show that the IVC project contributed to raising students&rsquo; awareness of how companies approach SDGs and adapt their products to different cultures. Students were also perceived to have developed intercultural knowledge, intercultural virtual teamwork, intercultural attitudes and intercultural awareness

Investigation of the 3-epi-25(OH)D3 of 25-hydroxyvitamin D3 in urban schoolchildren

Background: The physiological relevance C-3 epimer of 25-hydroxyvitamin D [3-epi-25(OH)D] is not well understood among youth. Objective: To assess whether demographic/physiologic characteristics were associated with 3-epi-25(OH)D3 concentrations in youth. Methods: Associations between 3-epi-25(OH)D3 and demographics, 3-epi-25(OH)D3, total 25-hydroxyvitamin (25(OH)D) (25(OH)D2 + 25(OH)D3), total cholesterol, HDL, LDL and triglycerides were examined in racially/ethnically diverse schoolchildren (n=682, 8-15yrs) at Boston-area urban schools. Results: Approximately 50% of participants had detectable 3-epi-25(OH)D3 (range 0.95-3.95 ng/mL). The percentage of 3-epi-25(OH)D3 of total 25(OH)D ranged from 2.5 to 17.0% (median 5.5%). Males were 38% more likely than females to have detectable 3-epi-25(OH)D3 concentrations. Both Asian and black race/ethnicity were associated with lower odds of having detectable 3-epi-25(OH)D3 compared to non-Hispanic white children ((Asian vs. white, OR 0.28, 95%CI 0.14-0.53; black vs. white, OR 0.38, 95%CI 0.23-0.63, pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Vitamin D supplementation and cardiometabolic risk factors among diverse schoolchildren: a randomized clinical trial

BACKGROUND: There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children. OBJECTIVES: We examined the effect of 3 different dosages of vitamin D on cardiometabolic risk factors among children at risk of deficiency. METHODS: Racially diverse schoolchildren aged 8-15 y were randomly assigned in a double-blind fashion to supplementation with 600, 1000, or 2000 IU vitamin D3/d for 6 mo. Changes in HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, and blood glucose over 6 mo and at 12 mo (6 mo post-supplementation) were assessed. Subgroup analyses were also performed by weight status and race. RESULTS: Among 604 children, 40.9% were vitamin D-inadequate at baseline (\u3c20 ng/mL; mean ± SD: 22.0 ± 6.8 ng/mL), 46.4% were overweight/obese, and 60.9% had ≥1 suboptimal blood lipids or glucose. Over 6 mo, serum 25-hydroxyvitamin D increased in all 3 dosage groups from baseline (mean ± SE change: 4.4 ± 0.6 ng/mL, 5.7 ± 0.7 ng/mL, and 10.7 ± 0.6 ng/mL for 600, 1000, and 2000 IU/d, respectively; P \u3c 0.001). Whereas HDL cholesterol and triglycerides increased in the 600 IU group (P = 0.002 and P = 0.02, respectively), LDL cholesterol and total cholesterol decreased across dosage groups. At 6 mo post-supplementation, HDL cholesterol remained elevated in the 600 and 1000 IU groups ( P \u3c 0.001 and P = 0.02, respectively) whereas triglycerides remained elevated in the 1000 and 2000 IU groups (P = 0.04 and P = 0.006, respectively). The suppression of LDL cholesterol and total cholesterol persisted in the 2000 IU group only (P = 0.04 and P \u3c 0.001, respectively). There were no significant changes in blood glucose and similar responses were observed overall by weight status and racial groups across dosages. CONCLUSIONS: Vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and total cholesterol, especially at the lower dosage of 600 IU/d, with several significant changes persisting during the post-supplementation period. Increases in triglycerides across dosage groups may be due to natural changes during adolescence warranting further study.This trial was registered at clinicaltrials.gov as NCT01537809

Plasma transfusion-transmission of Zika virus in mice and macaques.

BACKGROUND: Zika virus (ZIKV) epidemics with infections in pregnant women are associated with severe neurological disease in newborns. Although an arbovirus, ZIKV is also blood transfusion-transmitted (TT). Greater knowledge of the efficiency of ZIKV TT would aid decisions on testing and pathogen reduction technologies (PRT). STUDY DESIGN AND METHODS: Plasma units from ZIKV RNA-reactive blood donors were used to study infectivity in vitro, in mice, and in macaques. Furthermore, plasma units were subjected to PRT using amotosalen/ultraviolet light A (A/UVA) before transfusion. RESULTS: In vitro infectivity of ZIKV RNA-reactive plasma varied between 100 and 1000 international units (IU) of ZIKV RNA. Immunodeficient mice were more sensitive with as low as 32 IU sufficient to infect 50% of mice. 50-5500 IU of RNA led to TT in macaques using dose escalation of three different RNA-positive, seronegative plasma units. In contrast, RNA-reactive units collected postseroconversion were not infectious in macaques, even at a dose of 9 million IU RNA. After A/UVA PRT, transfusion of plasma containing up to 18 million IU was no longer infectious in vitro and did not result in ZIKV TT in macaques. CONCLUSION: Significant risks of ZIKV TT are likely confined to a relatively short viremic window before seroconversion, and that sensitive nucleic acid amplification testing likely identifies the majority of infectious plasma. PRT was demonstrated to be effective at preventing ZIKV TT. Considering that there is no approved ZIKV vaccine, these data are relevant to mitigate the risk of TT during the future ZIKV outbreaks