Dataset Information

Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

ABSTRACT: Background: Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines. Methods and Analysis: We will apply transcriptomic, proteomic, metabolomic, multiplex cytokine/chemokine, adenosine deaminase, and flow cytometry immune cell phenotyping to delineate early cellular and molecular signatures that correspond to vaccine immunogenicity. This approach will be applied to a neonatal cohort in The Gambia (N ~ 720) receiving at birth: (1) Hepatitis B (HepB) vaccine alone, (2) Bacille Calmette Guerin (BCG) vaccine alone, or (3) HepB and BCG vaccines, (4) HepB and BCG vaccines delayed till day 10 at the latest. Each study participant will have a baseline peripheral blood sample drawn at DOL0 and a second blood sample at DOL1,-3, or-7 as well as late timepoints to assess HepB vaccine immunogenicity. Blood will be fractionated via a "small sample big data" standard operating procedure that enables multiple downstream systems biology assays. We will apply both univariate and multivariate frameworks and multi-OMIC data integration to identify features associated with anti-Hepatitis B (anti-HB) titer, an established correlate of protection. Cord blood sample collection from a subset of participants will enable human in vitro modeling to test mechanistic hypotheses identified in silico regarding vaccine action. Maternal anti-HB titer and the infant microbiome will also be correlated with our findings which will be validated in a smaller cohort in Papua New Guinea (N ~ 80). Ethics and Dissemination: The study has been approved by The Gambia Government/MRCG Joint Ethics Committee and The Boston Children's Hospital Institutional Review Board. Ethics review is ongoing with the Papua New Guinea Medical Research Advisory Committee. All de-identified data will be uploaded to public repositories following submission of study output for publication. Feedback meetings will be organized to disseminate output to the study communities. Clinical Trial Registration: Clinicaltrials.gov Registration Number: NCT03246230.

SUBMITTER: Idoko OT

PROVIDER: S-EPMC7205022 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

Idoko Olubukola T OT Smolen Kinga K KK Wariri Oghenebrume O Imam Abdulazeez A Shannon Casey P CP Dibassey Tida T Diray-Arce Joann J Darboe Alansana A Strandmark Julia J Ben-Othman Rym R Odumade Oludare A OA McEnaney Kerry K Amenyogbe Nelly N Pomat William S WS van Haren Simon S Sanchez-Schmitz Guzmán G Brinkman Ryan R RR Steen Hanno H Hancock Robert E W REW Tebbutt Scott J SJ Richmond Peter C PC van den Biggelaar Anita H J AHJ Kollmann Tobias R TR Levy Ofer O Ozonoff Al A Kampmann Beate B

Frontiers in pediatrics 20200430

<b>Background:</b> Infection contributes to significant morbidity and mortality particularly in the very young and in low- and middle-income countries. While vaccines are a highly cost-effective tool against infectious disease little is known regarding the cellular and molecular pathways by which vaccines induce protection at an early age. Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new ...[more]

PMID: 32426309

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Project description:ObjectiveThis study examined the prevalence and predictors of maternal and newborn skin-to-skin contact at birth in Papua New Guinea.DesignData for the study was extracted from the 2016-18 Papua New Guinea Demographic and Health Survey. We included 6,044 women with birth history before the survey in the analysis. Percentages were used to summarise the prevalence of maternal and newborn skin-to-skin contact. A multivariable multilevel binary logistic regression was adopted to examine the predictors of maternal and newborn skin-to-skin contact. The results were presented using adjusted ORs (aORs), with their respective 95% confidence intervals (CIs). Statistical significance was set at p<0.05.SettingThe study was conducted in Papua New Guinea.ParticipantMothers with children under 5 years.Outcome measuresMother and newborn skin-to-skin contact.ResultsThe prevalence of mother and newborn skin-to-skin contact was 45.2% (95% CI=42.4 to 48.0). The odds of mother and newborn skin-to-skin contact was higher among women with primary education (aOR=1.38; 95% CI=1.03 to 1.83), women with four or more antenatal care attendance (aOR=1.27; 95% CI=1.01 to 1.61), those who delivered at the health facility (aOR=1.27; 95% CI=1.01 to 1.61), and women from communities with high socioeconomic status (aOR=1.45; 95% CI=1.11 to 1.90).ConclusionThe study has demonstrated that the prevalence of mother and newborn skin-to-skin contact in Papua New Guinea is low. Factors shown to be associated with mother and newborn skin-to-skin contact were maternal level of education, antenatal care attendance, health facility delivery, and community socioeconomic status. A concerted effort should be placed in improving maternal health service utilisation such as antenatal care attendance and skilled birth delivery, which subsequently lead to the practice of skin-to-skin contact. Also, women should be empowered through education as it has positive impact on their socioeconomic status and health service utilisation.

Project description:BackgroundChildren in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections.MethodsThis report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population.ResultsThis open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge.ConclusionLaboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization.Trial registrationClinicalTrials.gov CTN NCT01619462, retrospectively registered on May 28, 2012.

Dataset Information

Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

Publications

Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea.

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