Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn
Immunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Pr...
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00029/full |
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| author | Annette Scheid Annette Scheid Annette Scheid Annette Scheid Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Helen Christou Helen Christou Helen Christou Helen Christou Joann Diray-Arce Joann Diray-Arce Joann Diray-Arce Matthew A. Pettengill Matthew A. Pettengill Matthew A. Pettengill Sweta Joshi Sweta Joshi Ning Li Ning Li Ning Li Ilana Bergelson Ilana Bergelson Tobias Kollmann Tobias Kollmann David J. Dowling David J. Dowling Ofer Levy Ofer Levy Ofer Levy |
| author_facet | Annette Scheid Annette Scheid Annette Scheid Annette Scheid Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Helen Christou Helen Christou Helen Christou Helen Christou Joann Diray-Arce Joann Diray-Arce Joann Diray-Arce Matthew A. Pettengill Matthew A. Pettengill Matthew A. Pettengill Sweta Joshi Sweta Joshi Ning Li Ning Li Ning Li Ilana Bergelson Ilana Bergelson Tobias Kollmann Tobias Kollmann David J. Dowling David J. Dowling Ofer Levy Ofer Levy Ofer Levy |
| author_sort | Annette Scheid |
| collection | DOAJ |
| description | Immunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Program on Immunization, HBV is often given together with the live-attenuated vaccine Bacille Calmette–Guérin (BCG), known to activate multiple pattern-recognition receptors. Of note, some clinical studies suggest BCG can enhance efficacy of other vaccines in term newborns. However, little is known about whether BCG can shape Th-polarizing cytokine responses to HBV nor the age-dependency of such effects, including whether they may extend to the preterm. To characterize the effects of BCG on HBV immunogenicity, we studied individual and combined administration of these vaccines to cord newborn and adult human whole blood and mononuclear cells in vitro and to neonatal and adult mice in vivo. Compared to either BCG or HBV alone, (BCG + HBV) synergistically enhanced in vitro whole blood production of IL-1β, while (BCG + HBV) also promoted production of several cytokines/chemokines in all age groups, age-specific enhancement included IL-12p70 in the preterm and GM-CSF in the preterm and term. In human mononuclear cells, (BCG + HBV) enhanced mRNA expression of several genes including CSF2, which contributed to clustering of genes by vaccine treatment via principle component analysis. To assess the impact of BCG on HBV immunization, mice of three different age groups were immunized subcutaneously with, BCG, HBV, (BCG + HBV) into the same site; or BCG and HBV injected into separate sites. Whether injected into a separate site or at the same site, co-administration of BCG with HBV significantly enhanced anti-HBV IgG titers in mice immunized on day of life-0 or -7, respectively, but not in adult mice. In summary, our data demonstrate that innate and adaptive vaccine responses of preterm and term newborns are immunologically distinct. Furthermore, BCG or “BCG-like” adjuvants should be further studied as a promising adjuvantation approach to enhance immunogenicity of vaccines to protect these vulnerable populations. |
| first_indexed | 2024-12-19T06:51:23Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T06:51:23Z |
| publishDate | 2018-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-85da4ce05e644b358a962d00c8db13862022-12-21T20:31:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01910.3389/fimmu.2018.00029320130Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term NewbornAnnette Scheid0Annette Scheid1Annette Scheid2Annette Scheid3Francesco Borriello4Francesco Borriello5Francesco Borriello6Francesco Borriello7Francesco Borriello8Carlo Pietrasanta9Carlo Pietrasanta10Carlo Pietrasanta11Carlo Pietrasanta12Helen Christou13Helen Christou14Helen Christou15Helen Christou16Joann Diray-Arce17Joann Diray-Arce18Joann Diray-Arce19Matthew A. Pettengill20Matthew A. Pettengill21Matthew A. Pettengill22Sweta Joshi23Sweta Joshi24Ning Li25Ning Li26Ning Li27Ilana Bergelson28Ilana Bergelson29Tobias Kollmann30Tobias Kollmann31David J. Dowling32David J. Dowling33Ofer Levy34Ofer Levy35Ofer Levy36Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, ItalyWAO Center of Excellence, Naples, ItalyDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesNeonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, ItalyDepartment of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesDivision of Newborn Medicine, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United States0Medical Eli Lilly, Shanghai, ChinaDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United States1Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, BC, CanadaDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesPrecision Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, United StatesImmunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Program on Immunization, HBV is often given together with the live-attenuated vaccine Bacille Calmette–Guérin (BCG), known to activate multiple pattern-recognition receptors. Of note, some clinical studies suggest BCG can enhance efficacy of other vaccines in term newborns. However, little is known about whether BCG can shape Th-polarizing cytokine responses to HBV nor the age-dependency of such effects, including whether they may extend to the preterm. To characterize the effects of BCG on HBV immunogenicity, we studied individual and combined administration of these vaccines to cord newborn and adult human whole blood and mononuclear cells in vitro and to neonatal and adult mice in vivo. Compared to either BCG or HBV alone, (BCG + HBV) synergistically enhanced in vitro whole blood production of IL-1β, while (BCG + HBV) also promoted production of several cytokines/chemokines in all age groups, age-specific enhancement included IL-12p70 in the preterm and GM-CSF in the preterm and term. In human mononuclear cells, (BCG + HBV) enhanced mRNA expression of several genes including CSF2, which contributed to clustering of genes by vaccine treatment via principle component analysis. To assess the impact of BCG on HBV immunization, mice of three different age groups were immunized subcutaneously with, BCG, HBV, (BCG + HBV) into the same site; or BCG and HBV injected into separate sites. Whether injected into a separate site or at the same site, co-administration of BCG with HBV significantly enhanced anti-HBV IgG titers in mice immunized on day of life-0 or -7, respectively, but not in adult mice. In summary, our data demonstrate that innate and adaptive vaccine responses of preterm and term newborns are immunologically distinct. Furthermore, BCG or “BCG-like” adjuvants should be further studied as a promising adjuvantation approach to enhance immunogenicity of vaccines to protect these vulnerable populations.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00029/fullBacille Calmette–Guérinhepatitis B vaccinepretermnewborninnate cytokine profilesHBV-specific antibodies |
| spellingShingle | Annette Scheid Annette Scheid Annette Scheid Annette Scheid Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Francesco Borriello Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Carlo Pietrasanta Helen Christou Helen Christou Helen Christou Helen Christou Joann Diray-Arce Joann Diray-Arce Joann Diray-Arce Matthew A. Pettengill Matthew A. Pettengill Matthew A. Pettengill Sweta Joshi Sweta Joshi Ning Li Ning Li Ning Li Ilana Bergelson Ilana Bergelson Tobias Kollmann Tobias Kollmann David J. Dowling David J. Dowling Ofer Levy Ofer Levy Ofer Levy Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn Frontiers in Immunology Bacille Calmette–Guérin hepatitis B vaccine preterm newborn innate cytokine profiles HBV-specific antibodies |
| title | Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn |
| title_full | Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn |
| title_fullStr | Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn |
| title_full_unstemmed | Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn |
| title_short | Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn |
| title_sort | adjuvant effect of bacille calmette guerin on hepatitis b vaccine immunogenicity in the preterm and term newborn |
| topic | Bacille Calmette–Guérin hepatitis B vaccine preterm newborn innate cytokine profiles HBV-specific antibodies |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00029/full |
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