Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927

Project description:Much literature links individual feeding styles to infant feeding practices and growth; however, parents' feeding styles are not discrete and may vary by context. We use latent profile analysis (LPA) as a person-centered approach to categorize infant feeding style patterns, test factors predicting profile membership, and examine if profiles are associated with infant feeding and weight. Additionally, we test the impact of a responsive feeding intervention on profile membership and stability. Data come from 270 African-American women and infants participating in the Mothers and Others Study, an early life obesity prevention intervention. LPA was used to categorize mothers across five constructs (laissez-faire, pressuring, restrictive, responsive and indulgent) measured at 28-weeks gestation and 3- and 15-months postpartum. Adjusted multinomial regression and regression models test the characteristics associated with profile membership and the associations between profile membership and breastfeeding and infant weight-for-age z-score (WAZ). We identified two groups (Positive and Less Responsive) prenatally, an additional group (High Controlling) at 3 months and a fourth group (High Indulgent) at 15 months. Several characteristics differed between the groups, including maternal age, income and depressive symptoms, infant sex and temperament, and treatment group. Mothers in the Positive group were more likely to breastfeed at 3 months. Infants with mothers in the High Controlling group had higher WAZ at 15 months. The intervention was associated with more Positive feeding practices at 15 months and a greater likelihood of remaining in the Positive group across the study. LPA identified profiles that are associated with maternal and infant characteristics and treatment group and with better feeding practices and growth outcomes, providing preliminary evidence that early intervention promoting more responsive feeding profiles may improve infant outcomes.

Project description:South Africa has the highest prevalence of overweight/obesity in Sub-Saharan Africa. Assessing the effect of modifiable factors such as early infant feeding on growth velocity and overweight/obesity is therefore important. This paper aimed to assess the effect of infant feeding in the transitional period (12 weeks) on 12-24 week growth velocity amongst HIV unexposed children using WHO growth velocity standards and on the age and sex adjusted body mass index (BMI) Z-score distribution at 2 years.Data were from 3 sites in South Africa participating in the PROMISE-EBF trial. We calculated growth velocity Z-scores using the WHO growth standards and assessed feeding practices using 24-hour and 7-day recall data. We used quantile regression to study the associations between 12 week infant feeding and 12-24 week weight velocity (WVZ) with BMI-for-age Z-score at 2 years. We included the internal sample quantiles (70th and 90th centiles) that approximated the reference cut-offs of +2 (corresponding to overweight) and +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores.At the 2-year visit, 641 children were analysed (median age 22 months, IQR: 17-26 months). Thirty percent were overweight while 8.7% were obese. Children not breastfed at 12 weeks had higher 12-24 week mean WVZ and were more overweight and obese at 2 years. In the quantile regression, children not breastfed at 12 weeks had a 0.37 (95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th sample quantile compared to breast-fed children. This difference in BMI-for-age Z-score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI 0.41, 0.94) at the 90th quantile . The 12-24 week WVZ had a uniform independent effect across the same quantiles.This study demonstrates that the first 6 months of life is a critical period in the development of childhood overweight and obesity. Interventions targeted at modifiable factors such as early infant feeding practices may reduce the risks of rapid weight gain and subsequent childhood overweight/obesity.

Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 Whole blood collected 1 day post-vaccination with MVA85A or Candin placebo (82 samples)

Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927

Dataset Information

Feeding and developmental outcomes of infants in a South African community.

Publications

Feeding and developmental outcomes of infants in a South African community.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets