Newborn Vaccine ImmunogenicityEPIC-HIPCNCT03246230
Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
A study testing Hepatitis B vaccine (HBV) and Bacillus Calmette-Guérin (BCG) in people with Newborn Vaccine Immunogenicity, run by Boston Children's Hospital at 2 sites in 2 countries.
Trial summary
Infection is the most common cause of death in early life, especially for newborns and can be reduced by immunization but insufficient knowledge of how vaccines protect the very young limits their optimal use. Read more about this study
- Who is it for?
- Ages 0 days to 1 dayHealthy volunteers can take part
- Conditions the study is for
- Newborn Vaccine Immunogenicity
- What is being tested?
- Hepatitis B vaccine (HBV) and Bacillus Calmette-Guérin (BCG)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 911 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 6 Sep 2017to 29 Aug 2022
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 1 day
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- <24 hours of age
- >37 weeks gestational age
- HIV unexposed
- Healthy (no malformations, normal temperature range and vital signs for age)
Who cannot join
- Premature (<37 weeks gestational age)
- Hepatitis B antigen-positive mother
- HIV-positive or HIV-exposed
- Febrile, unstable vital signs
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Papua New Guinea1 site
Institute for Medical Research
Goroka, Eastern Highlands Province
About this study
Infection is the most common cause of death in early life, especially for newborns and can be reduced by immunization but insufficient knowledge of how vaccines protect the very young limits their optimal use. To gain insight into how vaccines induce protection of the most vulnerable, this National Institutes of Health (NIH)/National Institute of Allergy \& Infectious Diseases (NIAID)-funded Human Immunology Project Consortium (HIPC) study, based at Boston Children's Hospital and conducted by the Expanded Program on Immunization Consortium (EPIC), employs two novel approaches studying newborn responses to hepatitis B vaccine (HBV): (a) systems biology that uses technologies which comprehensively measure global changes in molecules such as transcriptomics (RNA) and proteomics (proteins), as well as cell composition of the blood and (b) use of human newborn blood components, collected prior to immunization, to model vaccine responses in vitro (outside the body). Characterizing vaccine-induced molecular patterns ("signatures") that correspond to vaccine-mediated protection will accelerate development and optimization of vaccines against early life infections of major global health importance.
Read the detailed description
While the greatest number of vaccines is administered to the very young, vaccine preventable infections remain a major cause of morbidity and mortality, especially for the newborn. To improve vaccine-mediated protection early in life, the investigators will identify biomarkers that predict protective efficacy and garner insight into the underlying mechanisms of vaccine-mediated protection. Systems biology approaches ("OMICs") applied to vaccinology, i.e., systems vaccinology, has revolutionized the field with an unbiased identification of pathways relevant to vaccine-induced immune responses. However, thus far systems vaccinology has focused primarily on adults, with few studies conducted in children and infants, and none in newborns. This study will bridge this gap by conducting a comprehensive systems vaccinology study in newborns. Specifically, the investigators will determine the molecular pathways that are associated with successful neonatal immunization with hepatitis B virus vaccine (HBV). HBV is the ideal model because i) it is highly (>90%) effective; ii) it has a well-established correlate of protection (CoP; anti-hepatitis surface antigen antibody (anti-HBs)); iii) there is substantial variation in anti-HBs titers and quantifiable inter-subject variability is essential for systems biological approaches; iv) it is highly relevant as HBV is given at birth in the U.S. and most developing countries; v) it is amenable to in vivo manipulation with another regularly administered neonatal vaccine, Bacille Calmette-Guérin (BCG), which will greatly enhance detection of relevant signatures. As complex networks of functional interactions among genes and proteins drive the response to immunization, the investigators will integrate transcriptomic, proteomic and immune phenotyping approaches. Importantly, the investigators have successfully adapted these experimental platforms to be fully operational within the small blood volumes obtainable in newborns. The investigators have also developed in vitro systems amenable to experimental manipulation on the cellular and molecular level to identify cause-effect relationships. Pilot data prove feasibility of collecting the relevant high-quality samples according to stringent standard operating procedures, processing them and delivering cogent OMIC data suggesting vaccine-specific 'signatures' in the human newborn. This HIPC will identify biomarkers of neonatal HBV immunogenicity by pursuing the following Overall Specific Aims:
- Aim 1. Characterize pre-vaccine OMIC and immune signatures in vivo that predict immunogenicity of HBV in human newborns. In adult systems vaccinology studies, baseline immune status of vaccine recipients predicted vaccine immunogenicity at least as well or even better than changes induced by the vaccine. For Aim 1 the investigators will determine the pre-vaccine (Day 0) characteristics of whole blood gene expression, plasma proteome as well as the composition of the white blood cell compartment and their functional status in correlation with the HBV-induced neonatal antibody response.
- Aim 2. Characterize the post-vaccine impact of HBV on OMIC and immune signatures in vivo that predict immunogenicity of HBV in human newborns. In adults, analysis of vaccine-induced signatures (i.e. post-vaccine) has provided new insights for several vaccines, including HBV. The investigators will for the first time apply this approach to newborns and expand it by manipulating the neonatal response to HBV in vivo by co-administering BCG, as it substantially changes immunogenicity of HBV thereby testing cause-effect relationships in vivo. For Aim 2 the investigators will characterize whole blood gene expression and the plasma and leukocyte proteome as well as white blood cell composition and functional status at Days 1, -3 and -7 postvaccine contrasting infants that received nothing (delayed vaccines to 7 days of age), HBV, BCG or (HBV + BCG) at birth and correlate this with anti-HBs titers.
- Aim 3. Interrogate functional correlations identified in silico via novel human in vitro platforms that accurately model age-specific vaccine responses and are amenable to a wide range of experimental manipulation allowing mechanistic cause-effect relationships to be probed on the molecular level.
Overall, these integrated studies will identify vaccine-induced molecular pathways correlating with protective immune responses in newborns and will generate and test new mechanistic hypotheses regarding vaccine action in vivo and in vitro. This study will ultimately inform, accelerate and optimize early life immunization resulting in major public health benefit.
- Conditions
- Newborn Vaccine Immunogenicity
- Being tested
- Hepatitis B vaccine (HBV), Bacillus Calmette-Guérin (BCG)
- Keywords
- newborn vaccine responses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatitis B vaccine (HBV)Biological
Licensed pediatric HBV vaccine will be administered at birth (Day of Life 0) or delayed to Day of Life 7.
Bacillus Calmette-Guérin (BCG)Biological
Licensed BCG vaccine will be administered at birth (Day of Life 0) or delayed to Day of Life 7.
| Study group | Role | What they receive |
|---|---|---|
| NO VACCINES AT BIRTH | No intervention | These will be newborns who will not receive any vaccines at birth and will have delayed immunization with catch-up (i.e., HBV, BCG and polio vaccine) by Day of Life 7. |
| HBV VACCINE AT BIRTH | Other | Participants in this arm will receive licensed hepatitis B vaccine (HBV) at birth (Day of Life (DOL)-0) with catch up immunization (i.e., BCG and polio vaccine) at DOL-1, -3, or -7. Receives: Biological: Hepatitis B vaccine (HBV) |
| BCG VACCINE AT BIRTH | Other | Participants in this arm will receive licensed Bacillus Calmette-Guérin (BCG) vaccine at birth (Day of Life(DOL)-0) with catch up immunization (i.e., HBV and polio vaccine) at DOL-1, -3 or- 7. Receives: Biological: Bacillus Calmette-Guérin (BCG) |
| (HBV + BCG) VACCINES AT BIRTH | Other | Participants in this arm will receive licensed hepatitis B vaccine (HBV) and licensed Bacillus Calmette-Guérin (BCG) vaccine at birth (Day of Life (DOL- 0) with catch up immunization (i.e., polio vaccine) at DOL-1, -3, or -7. Receives: Biological: Hepatitis B vaccine (HBV); Biological: Bacillus Calmette-Guérin (BCG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular signature correlating with anti-hepatitis B vaccine antibody response
We will employ bioinformatics to define molecular signatures correlating with anti-HBV responses
Measured: 1 month of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2017
- Study start6 Sep 2017
- Primary completion29 Aug 2022
- Study completion29 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Newborn Vaccine ImmunogenicityStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Newborn infants will have delayed immunization, with catch-up immunization at day of life 7 (DOL7), or immunization at birth with hepatitis B vaccine (HBV), Bacille Calmette-Guérin (BCG) or (HBV +BCG). All participants will have peripheral blood collected at birth (DOL0) and each group will be divided into sub-groups with follow-up peripheral blood collection at DOL1, DOL3, or DOL7.
- Masking
- None (open label)
- Enrolment
- 911 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council Unit, The Gambia, University of British Columbia, Institute for Medical Research, Papua New Guinea, The University of Western Australia
- Responsible party
- Principal investigator, Ofer Levy, Boston Children's Hospital
- Investigators
- Ofer Levy, MD, PhD, Principal investigator, Boston Children's HospitalTobias R Kollmann, MD, PhD, Study director, The University of Western AustraliaBeate Kampmann, MD, PhD, Study chair, Medical Research Council (MRC) Gambia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03246230
- Sponsor's protocol ID
- IRB-P00024239
- Acronym
- EPIC-HIPC
- Status last verified
- Nov 2023
- First submitted
- 4 Aug 2017
- Last updated
- 6 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Amenyogbe N, Levy O, Kollmann TR. Systems vaccinology: a promise for the young and the poor. Philos Trans R Soc Lond B Biol Sci. 2015 Jun 19;370(1671):20140340. doi: 10.1098/rstb.2014.0340.
PubMed 25964462Lee AH, Shannon CP, Amenyogbe N, Bennike TB, Diray-Arce J, Idoko OT, Gill EE, Ben-Othman R, Pomat WS, van Haren SD, Cao KL, Cox M, Darboe A, Falsafi R, Ferrari D, Harbeson DJ, He D, Bing C, Hinshaw SJ, Ndure J, Njie-Jobe J, Pettengill MA, Richmond PC, Ford R, Saleu G, Masiria G, Matlam JP, Kirarock W, Roberts E, Malek M, Sanchez-Schmitz G, Singh A, Angelidou A, Smolen KK; EPIC Consortium; Brinkman RR, Ozonoff A, Hancock REW, van den Biggelaar AHJ, Steen H, Tebbutt SJ, Kampmann B, Levy O, Kollmann TR. Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nat Commun. 2019 Mar 12;10(1):1092. doi: 10.1038/s41467-019-08794-x.
PubMed 30862783Checkervarty AK, Shannon CP, Blimkie TM, Dhillon BK, Falsafi R, Angelidou A, Diray-Arce J, Bennike TB, Archer NM, Idoko OT, McEnaney K, Ozonoff A, Odumade OA, Ben-Othman R, Smolen KK, Steen H; EPIC-HIPC Consortium; Kampmann B, Kollmann TR, Levy O, Lee AH, Hancock REW, Tebbutt SJ. Newborns with sickle cell trait have distinct peripheral blood molecular signatures across the first week of life. Blood Red Cells Iron. 2026 Jun;2(2):100051. doi: 10.1016/j.brci.2026.100051. Epub 2026 Mar 31.
PubMed 42368247Dhillon BK, Blimkie TM, Idoko OT, Ford R, Angelidou A, Ben-Othman R, Montante S, Amenyogbe N, Dibassey T, Diray-Arce J, Falsafi R, Imam A, McEnaney K, Odumade OA, Ozonoff A, Pomat WS, Richmond PC, Smolen KK, Wariri O; EPIC-HIPC Consortium; Levy O, van den Biggelaar AHJ, Kampmann B, Kollmann TR, Lee AHY, Hancock REW. Population-specific heterogeneity in ontogeny of the broadly-conserved blood transcriptional program during the first week of life. Nat Commun. 2026 Jun 1;17(1):5673. doi: 10.1038/s41467-026-73244-4.
PubMed 42225675Diray-Arce J, Syphurs C, Hoch A, McEnaney K, Smolen KK, Wariri O, Imam A, Dibassey T, Cole F, Ceesay F, Darboe A, Pomat WS, Ford R, Masiria G, Joseph D, Jude J, Ben-Othman R, Shannon CP, Thomas S, Leroux-Roels G, Clement F, Waerlop G, McLoughlin C, Vignolo SM, Rao S, Amenyogbe N; EPIC Consortium; Odumade O, Angelidou A, Tebbutt SJ, Marchant A, Kollmann TR, Levy O, Richmond PC, van den Biggelaar AHJ, Kampmann B, Idoko OT, Ozonoff A. A randomized prospective study of neonatal hepatitis B vaccine immunogenicity in The Gambia and Papua New Guinea. J Allergy Clin Immunol Glob. 2026 Feb 6;5(3):100653. doi: 10.1016/j.jacig.2026.100653. eCollection 2026 May.
PubMed 41809112Montante S, Ben-Othman R, Amenyogbe N, Angelidou A, van den Biggelaar A, Cai B, Chen Y, Darboe A, Diray-Arce J, Ford R, Idoko O, Lee A, Lo M, McEnaney K, Malek M, Martino D, Masiria G, Odumade OA, Pomat W, Shannon C, Smolen K, Consortium TE, Ozonoff A, Richmond P, Tebbutt S, Levy O, Kampmann B, Brinkman R, Kollmann T. Breastfeeding and Neonatal Age Influence Neutrophil-Driven Ontogeny of Blood Cell Populations in the First Week of Human Life. J Immunol Res. 2024 Jul 23;2024:1117796. doi: 10.1155/2024/1117796. eCollection 2024.
PubMed 39081632Idoko OT, Smolen KK, Wariri O, Imam A, Shannon CP, Dibassey T, Diray-Arce J, Darboe A, Strandmark J, Ben-Othman R, Odumade OA, McEnaney K, Amenyogbe N, Pomat WS, van Haren S, Sanchez-Schmitz G, Brinkman RR, Steen H, Hancock REW, Tebbutt SJ, Richmond PC, van den Biggelaar AHJ, Kollmann TR, Levy O, Ozonoff A, Kampmann B. 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. Front Pediatr. 2020 Apr 30;8:197. doi: 10.3389/fped.2020.00197. eCollection 2020.
PubMed 32426309