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
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 prote...
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| Published in: | Frontiers in pediatrics Vol. 8; p. 197 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Frontiers Media S.A
30-04-2020
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| Abstract | 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.
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 (
~ 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
modeling to test mechanistic hypotheses identified
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 (
~ 80).
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.
: Clinicaltrials.gov Registration Number: NCT03246230. |
|---|---|
| AbstractList | 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 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. 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 ( ~ 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 modeling to test mechanistic hypotheses identified 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 ( ~ 80). 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. : Clinicaltrials.gov Registration Number: NCT03246230. 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 |
| Author | van den Biggelaar, Anita H J Darboe, Alansana Dibassey, Tida Diray-Arce, Joann van Haren, Simon Amenyogbe, Nelly Ozonoff, Al Imam, Abdulazeez Kollmann, Tobias R Levy, Ofer Tebbutt, Scott J Shannon, Casey P McEnaney, Kerry Kampmann, Beate Hancock, Robert E W Smolen, Kinga K Pomat, William S Odumade, Oludare A Brinkman, Ryan R Strandmark, Julia Steen, Hanno Ben-Othman, Rym Wariri, Oghenebrume Idoko, Olubukola T Richmond, Peter C Sanchez-Schmitz, Guzmán |
| AuthorAffiliation | 13 Department of Medical Genetics, University of British Columbia , Vancouver, BC , Canada 16 Centre for Heart Lung Innovation, University of British Columbia , Vancouver, BC , Canada 11 Papua New Guinea Institute of Medical Research , Goroka , Papua New Guinea 1 Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine , Fajara , Gambia 6 PROOF Centre of Excellence , Vancouver, BC , Canada 2 Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital , Boston, MA , United States 4 The Vaccine Centre, London School of Hygiene and Tropical Medicine , London , United Kingdom 7 Department of Pediatrics, BC Children's Hospital, University of British Columbia , Vancouver, BC , Canada 5 Harvard Medical School , Boston, MA , United States 8 Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital , Boston, MA , United States 12 BC Cancer Agency , Vancouver, BC , Canada 9 Department of |
| AuthorAffiliation_xml | – name: 15 Department of Microbiology & Immunology, University of British Columbia , Vancouver, BC , Canada – name: 13 Department of Medical Genetics, University of British Columbia , Vancouver, BC , Canada – name: 8 Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital , Boston, MA , United States – name: 2 Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital , Boston, MA , United States – name: 14 Department of Pathology, Boston Children's Hospital , Boston, MA , United States – name: 1 Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine , Fajara , Gambia – name: 4 The Vaccine Centre, London School of Hygiene and Tropical Medicine , London , United Kingdom – name: 19 Broad Institute of MIT & Harvard , Cambridge, MA , United States – name: 5 Harvard Medical School , Boston, MA , United States – name: 16 Centre for Heart Lung Innovation, University of British Columbia , Vancouver, BC , Canada – name: 3 CIH LMU Center for International Health, Medical Center of the University of Munich (LMU) , Munich , Germany – name: 7 Department of Pediatrics, BC Children's Hospital, University of British Columbia , Vancouver, BC , Canada – name: 12 BC Cancer Agency , Vancouver, BC , Canada – name: 18 Division of Pediatrics, School of Medicine, Perth Children's Hospital, University of Western Australia , Nedlands, WA , Australia – name: 17 Division of Respiratory Medicine, Department of Medicine, UBC , Vancouver, BC , Canada – name: 10 Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Nedlands, WA , Australia – name: 9 Department of Cardiology, Boston Children's Hospital , Boston, MA , United States – name: 6 PROOF Centre of Excellence , Vancouver, BC , Canada – name: 11 Papua New Guinea Institute of Medical Research , Goroka , Papua New Guinea |
| Author_xml | – sequence: 1 givenname: Olubukola T surname: Idoko fullname: Idoko, Olubukola T organization: The Vaccine Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom – sequence: 2 givenname: Kinga K surname: Smolen fullname: Smolen, Kinga K organization: Harvard Medical School, Boston, MA, United States – sequence: 3 givenname: Oghenebrume surname: Wariri fullname: Wariri, Oghenebrume organization: Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia – sequence: 4 givenname: Abdulazeez surname: Imam fullname: Imam, Abdulazeez organization: Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia – sequence: 5 givenname: Casey P surname: Shannon fullname: Shannon, Casey P organization: PROOF Centre of Excellence, Vancouver, BC, Canada – sequence: 6 givenname: Tida surname: Dibassey fullname: Dibassey, Tida organization: Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia – sequence: 7 givenname: Joann surname: Diray-Arce fullname: Diray-Arce, Joann organization: Harvard Medical School, Boston, MA, United States – sequence: 8 givenname: Alansana surname: Darboe fullname: Darboe, Alansana organization: Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia – sequence: 9 givenname: Julia surname: Strandmark fullname: Strandmark, Julia organization: Vaccines and Immunity Theme, Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia – sequence: 10 givenname: Rym surname: Ben-Othman fullname: Ben-Othman, Rym organization: Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada – sequence: 11 givenname: Oludare A surname: Odumade fullname: Odumade, Oludare A organization: Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States – sequence: 12 givenname: Kerry surname: McEnaney fullname: McEnaney, Kerry organization: Department of Cardiology, Boston Children's Hospital, Boston, MA, United States – sequence: 13 givenname: Nelly surname: Amenyogbe fullname: Amenyogbe, Nelly organization: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia – sequence: 14 givenname: William S surname: Pomat fullname: Pomat, William S organization: Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea – sequence: 15 givenname: Simon surname: van Haren fullname: van Haren, Simon organization: Harvard Medical School, Boston, MA, United States – sequence: 16 givenname: Guzmán surname: Sanchez-Schmitz fullname: Sanchez-Schmitz, Guzmán organization: Harvard Medical School, Boston, MA, United States – sequence: 17 givenname: Ryan R surname: Brinkman fullname: Brinkman, Ryan R organization: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada – sequence: 18 givenname: Hanno surname: Steen fullname: Steen, Hanno organization: Department of Pathology, Boston Children's Hospital, Boston, MA, United States – sequence: 19 givenname: Robert E W surname: Hancock fullname: Hancock, Robert E W organization: Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, Canada – sequence: 20 givenname: Scott J surname: Tebbutt fullname: Tebbutt, Scott J organization: Division of Respiratory Medicine, Department of Medicine, UBC, Vancouver, BC, Canada – sequence: 21 givenname: Peter C surname: Richmond fullname: Richmond, Peter C organization: Division of Pediatrics, School of Medicine, Perth Children's Hospital, University of Western Australia, Nedlands, WA, Australia – sequence: 22 givenname: Anita H J surname: van den Biggelaar fullname: van den Biggelaar, Anita H J organization: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia – sequence: 23 givenname: Tobias R surname: Kollmann fullname: Kollmann, Tobias R organization: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia – sequence: 24 givenname: Ofer surname: Levy fullname: Levy, Ofer organization: Broad Institute of MIT & Harvard, Cambridge, MA, United States – sequence: 25 givenname: Al surname: Ozonoff fullname: Ozonoff, Al organization: Harvard Medical School, Boston, MA, United States – sequence: 26 givenname: Beate surname: Kampmann fullname: Kampmann, Beate organization: The Vaccine Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32426309$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3389_fimmu_2021_578700 crossref_primary_10_3389_fimmu_2022_1043375 crossref_primary_10_1038_s41590_021_01054_5 crossref_primary_10_1136_bmjgh_2021_006419 crossref_primary_10_3390_vaccines9060579 crossref_primary_10_1136_bmjopen_2021_053720 crossref_primary_10_3390_metabo10120492 crossref_primary_10_1002_cyto_a_24776 crossref_primary_10_3389_fimmu_2020_578505 |
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| Copyright | Copyright © 2020 Idoko, Smolen, Wariri, Imam, Shannon, Dibassey, Diray-Arce, Darboe, Strandmark, Ben-Othman, Odumade, McEnaney, Amenyogbe, Pomat, van Haren, Sanchez-Schmitz, Brinkman, Steen, Hancock, Tebbutt, Richmond, van den Biggelaar, Kollmann, Levy, Ozonoff and Kampmann. Copyright © 2020 Idoko, Smolen, Wariri, Imam, Shannon, Dibassey, Diray-Arce, Darboe, Strandmark, Ben-Othman, Odumade, McEnaney, Amenyogbe, Pomat, van Haren, Sanchez-Schmitz, Brinkman, Steen, Hancock, Tebbutt, Richmond, van den Biggelaar, Kollmann, Levy, Ozonoff and Kampmann. 2020 Idoko, Smolen, Wariri, Imam, Shannon, Dibassey, Diray-Arce, Darboe, Strandmark, Ben-Othman, Odumade, McEnaney, Amenyogbe, Pomat, van Haren, Sanchez-Schmitz, Brinkman, Steen, Hancock, Tebbutt, Richmond, van den Biggelaar, Kollmann, Levy, Ozonoff and Kampmann |
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| Keywords | systems biology vaccine newborn markers OMICS immunogenicity |
| Language | English |
| License | Copyright © 2020 Idoko, Smolen, Wariri, Imam, Shannon, Dibassey, Diray-Arce, Darboe, Strandmark, Ben-Othman, Odumade, McEnaney, Amenyogbe, Pomat, van Haren, Sanchez-Schmitz, Brinkman, Steen, Hancock, Tebbutt, Richmond, van den Biggelaar, Kollmann, Levy, Ozonoff and Kampmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors have contributed equally to this work and shares senior authorship Edited by: Eric Giannoni, CHU de Lausanne (CHUV), Switzerland Reviewed by: Riccardo Castagnoli, University of Pavia, Italy; Claus Klingenberg, Arctic University of Norway, Norway This article was submitted to Pediatric Immunology, a section of the journal Frontiers in Pediatrics |
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| References | 33313031 - Front Pediatr. 2020 Nov 17;8:610461 Okwo-Bele (B9) 2011; 29 Amenyogbe (B16) 2015; 370 Ozawa (B6) 2017; 95 Idoko (B5) 2013; 88 Hagan (B15) 2018; 10 Ozawa (B4) 2013; 9 Sanchez-Schmitz (B27) 2018; 9 Kollmann (B14) 2017; 46 Kagina (B30) 2009; 27 Schillie (B18) 2013; 31 Hu (B24) 2008; 26 Tsang (B21) 2015; 36 Ritz (B23) 2013; 31 Van Herck (B25) 2008; 27 Fourati (B26) 2016; 7 Newell (B29) 2010; 120 Stubbe (B20) 2006; 177 Ota (B22) 2002; 168 Henderson (B10) 2011; 29 Lee (B17) 2019; 10 Bagcchi (B11) 2016; 16 Garon (B12) 2016; 15 Birn (B8) 2011; 16 Patel (B13) 2016; 53 (B2) 2017; 390 (B1) 2017 Delany (B7) 2014; 6 Jack (B19) 1999; 179 Hart (B28) 2013; 20 Duclos (B3) 2009; 9 |
| References_xml | – volume: 27 start-page: 5488 year: 2009 ident: B30 article-title: Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response publication-title: Vaccine. doi: 10.1016/j.vaccine.2009.06.103 contributor: fullname: Kagina – volume: 9 start-page: 1774 year: 2013 ident: B4 article-title: Public trust and vaccine acceptance–international perspectives publication-title: Hum Vaccin Immunother. doi: 10.4161/hv.24961 contributor: fullname: Ozawa – volume: 370 year: 2015 ident: B16 article-title: Systems vaccinology: a promise for the young and the poor publication-title: Philos Trans R Soc Lond B Biol Sci. doi: 10.1098/rstb.2014.0340 contributor: fullname: Amenyogbe – volume: 120 start-page: 1836 year: 2010 ident: B29 article-title: Identification of a B cell signature associated with renal transplant tolerance in humans publication-title: J Clin Invest. doi: 10.1172/JCI39933 contributor: fullname: Newell – volume: 46 start-page: 350 year: 2017 ident: B14 article-title: Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny publication-title: Immunity. doi: 10.1016/j.immuni.2017.03.009 contributor: fullname: Kollmann – volume: 29 year: 2011 ident: B9 article-title: The expanded programme on immunization: a lasting legacy of smallpox eradication publication-title: Vaccine. doi: 10.1016/j.vaccine.2012.01.080 contributor: fullname: Okwo-Bele – volume: 390 start-page: 1151 year: 2017 ident: B2 article-title: Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016 publication-title: Lancet. doi: 10.1016/S0140-6736(17)32152-9 – volume: 29 year: 2011 ident: B10 article-title: The eradication of smallpox–an overview of the past, present, and future publication-title: Vaccine doi: 10.1016/j.vaccine.2011.06.080 contributor: fullname: Henderson – volume: 31 start-page: 2506 year: 2013 ident: B18 article-title: Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review publication-title: Vaccine. doi: 10.1016/j.vaccine.2012.12.012 contributor: fullname: Schillie – volume: 16 start-page: 644 year: 2016 ident: B11 article-title: Polio endgame: overcoming the final barriers publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(16)30093-7 contributor: fullname: Bagcchi – volume: 7 start-page: 10369 year: 2016 ident: B26 article-title: Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination publication-title: Nat Commun. doi: 10.1038/ncomms10369 contributor: fullname: Fourati – volume: 16 start-page: 591 year: 2011 ident: B8 article-title: Small(pox) success? publication-title: Cien Saude Colet. doi: 10.1590/S1413-81232011000200022 contributor: fullname: Birn – volume: 20 start-page: 970 year: 2013 ident: B28 article-title: Calculating sample size estimates for RNA sequencing data publication-title: J Comput Biol. doi: 10.1089/cmb.2012.0283 contributor: fullname: Hart – volume: 9 year: 2009 ident: B3 article-title: Global immunization: status, progress, challenges and future publication-title: BMC Int Health Hum Rights. doi: 10.1186/1472-698X-9-S1-S2 contributor: fullname: Duclos – volume: 95 start-page: 629 year: 2017 ident: B6 article-title: Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001-2020 publication-title: Bull World Health Organ. doi: 10.2471/BLT.16.178475 contributor: fullname: Ozawa – volume: 177 start-page: 8185 year: 2006 ident: B20 article-title: Antigen-specific central memory CD4+ T lymphocytes produce multiple cytokines and proliferate in vivo in humans publication-title: J Immunol. doi: 10.4049/jimmunol.177.11.8185 contributor: fullname: Stubbe – volume: 26 start-page: 6064 year: 2008 ident: B24 article-title: Influence of maternal antibody against hepatitis B surface antigen on active immune response to hepatitis B vaccine in infants publication-title: Vaccine. doi: 10.1016/j.vaccine.2008.09.014 contributor: fullname: Hu – year: 2017 ident: B1 publication-title: Levels and Trends in Child Mortality – volume: 15 start-page: 693 year: 2016 ident: B12 article-title: Polio endgame: the global switch from tOPV to bOPV publication-title: Expert Rev Vaccines. doi: 10.1586/14760584.2016.1140041 contributor: fullname: Garon – volume: 27 start-page: 861 year: 2008 ident: B25 article-title: Benefits of early hepatitis B immunization programs for newborns and infants publication-title: Pediatr Infect Dis J. doi: 10.1097/INF.0b013e318173966f contributor: fullname: Van Herck – volume: 31 start-page: 3098 year: 2013 ident: B23 article-title: Non-specific effect of Bacille Calmette-Guerin vaccine on the immune response to routine immunisations publication-title: Vaccine. doi: 10.1016/j.vaccine.2013.03.059 contributor: fullname: Ritz – volume: 53 start-page: 28 year: 2016 ident: B13 article-title: Polio eradication and endgame plan - victory within grasp publication-title: Indian Pediatr. contributor: fullname: Patel – volume: 10 start-page: a028894 year: 2018 ident: B15 article-title: Will systems biology deliver its promise and contribute to the development of new or improved vaccines? From data to understanding through systems biology publication-title: Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a028894 contributor: fullname: Hagan – volume: 36 start-page: 479 year: 2015 ident: B21 article-title: Utilizing population variation, vaccination, and systems biology to study human immunology publication-title: Trends Immunol doi: 10.1016/j.it.2015.06.005 contributor: fullname: Tsang – volume: 168 start-page: 919 year: 2002 ident: B22 article-title: Influence of Mycobacterium bovis bacillus calmette-guerin on antibody and cytokine responses to human neonatal vaccination publication-title: J Immunol. doi: 10.4049/jimmunol.168.2.919 contributor: fullname: Ota – volume: 10 start-page: 1092 year: 2019 ident: B17 article-title: Dynamic molecular changes during the first week of human life follow a robust developmental trajectory publication-title: Nat Commun. doi: 10.1038/s41467-019-08794-x contributor: fullname: Lee – volume: 9 start-page: 2634 year: 2018 ident: B27 article-title: Microphysiologic human tissue constructs reproduce autologous age-specific BCG and HBV primary immunization in vitro publication-title: Front Immunol. doi: 10.3389/fimmu.2018.02634 contributor: fullname: Sanchez-Schmitz – volume: 179 start-page: 489 year: 1999 ident: B19 article-title: What level of hepatitis B antibody is protective? publication-title: J Infect Dis. doi: 10.1086/314578 contributor: fullname: Jack – volume: 88 start-page: 414 year: 2013 ident: B5 article-title: Impact, challenges, and future projections of vaccine trials in Africa publication-title: Am J Trop Med Hyg. doi: 10.4269/ajtmh.12-0576 contributor: fullname: Idoko – volume: 6 start-page: 708 year: 2014 ident: B7 article-title: Vaccines for the 21st century publication-title: EMBO Mol Med. doi: 10.1002/emmm.201403876 contributor: fullname: Delany |
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| Title | 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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