Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity

NCT03246230 | Completed

• 1 other identifier: IRB-P00024239
• Study Type: interventional
• Target: 911
• Locations: 2 countries
• Sites: 2

Brief 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. 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.

Conditions

Newborn Vaccine Immunogenicity

Keywords

newborn vaccine responses

Outcome Measures

Primary Outcomes (1)

• Molecular signature correlating with anti-hepatitis B vaccine antibody response

  We will employ bioinformatics to define molecular signatures correlating with anti-HBV responses

  1 month of age

Study Arms (4)

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.

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.

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.

Biological: Hepatitis B vaccine (HBV); Biological: Bacillus Calmette-Guérin (BCG)

Interventions

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.

(HBV + BCG) VACCINES AT BIRTH; HBV VACCINE AT BIRTH

Bacillus Calmette-Guérin (BCG) BIOLOGICAL

Licensed BCG vaccine will be administered at birth (Day of Life 0) or delayed to Day of Life 7.

(HBV + BCG) VACCINES AT BIRTH; BCG VACCINE AT BIRTH

Eligibility Criteria

• Age: 0 Days - 1 Day
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• \<24 hours of age
• \>37 weeks gestational age
• HIV unexposed
• Healthy (no malformations, normal temperature range and vital signs for age)

You may not qualify if:

• Premature (\<37 weeks gestational age)
• Hepatitis B antigen-positive mother
• HIV-positive or HIV-exposed
• Febrile, unstable vital signs

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Medical Research Council Unit, The Gambia: collaborator
• University of British Columbia: collaborator
• Institute for Medical Research, Papua New Guinea: collaborator
• The University of Western Australia: collaborator

Study Sites (2)

Institute for Medical Research

Goroka, Eastern Highlands Province, Papua New Guinea

Location

Medical Research Council Unit, The Gambia

Fajara, 000273, The Gambia

Location

Related Publications (4)

• 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.

  PMID: 25964462 BACKGROUND

• Lee 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.

  PMID: 30862783 BACKGROUND

• Montante 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.

  PMID: 39081632 DERIVED

• Idoko 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.

  PMID: 32426309 DERIVED

Related Links

• Human Immunology Project Consortium/National Institute of Allergy \& Infectious Diseases
• Precision Vaccines Program, Boston Children's Hospital
• Data, Tools \& Resources related to NIH/NIAID Human Immunology Project Consortium

MeSH Terms

Interventions

Hepatitis B Vaccines

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Ofer Levy, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Tobias R Kollmann, MD, PhD

  The University of Western Australia

  STUDY DIRECTOR

• Beate Kampmann, MD, PhD

  Medical Research Council (MRC) Gambia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Model Details: 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.

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 11, 2017
• Study Start: September 6, 2017
• Primary Completion: August 29, 2022
• Study Completion: August 29, 2022
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1); TH (1)