PMID- 35105495 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20220311 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 40 IP - 9 DP - 2022 Feb 23 TI - Hepatitis B vaccine co-administration influences the heterologous effects of neonatal BCG vaccination in a sex-differential manner. PG - 1334-1341 LID - S0264-410X(22)00020-2 [pii] LID - 10.1016/j.vaccine.2022.01.005 [doi] AB - INTRODUCTION: Bacille Calmette-Guerin (BCG) and hepatitis B (HBV) vaccines are frequently given concomitantly at birth. Neonatal BCG vaccination induces off-target immunological effects. Whether HBV vaccine has immunomodulatory effects is unknown. As off-target effects might vary when vaccines are given simultaneously, this randomised controlled trial aimed to evaluate the influence of neonatal vaccination with BCG and/or HBV on heterologous immune responses. METHODS: A total of 185 neonates in Australia were randomised to receive either neonatal BCG-Denmark vaccine, HBV vaccine, both (BCG + HBV group), or none (No vaccine group). In-vitro responses to heterologous stimulants were assessed 7 days after vaccination. The influence of (i) randomisation group and (ii) sex on interferon-gamma (IFN-gamma), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-alpha) responses was analysed using linear regression. RESULTS: Overall, BCG vaccination alone or with HBV co-administration reduced IFN-gamma and MCP-1 responses to heterologous stimulants. HBV vaccination alone did not alter heterologous cytokine responses. In general, males produced more IFN-gamma and TNF-alpha than females. We observed a sex-differential effect in relation to the influence of HBV co-administration on the effect of BCG on heterologous responses. Compared with males in the No vaccine group, males in the BCG + HBV group had lower IFN-gamma and MCP-1 responses. In contrast, compared with females in the No vaccine group, females in the BCG group had higher IFN-gamma response and lower MCP-1 responses. CONCLUSION: Neonatal BCG vaccination resulted in lower cytokine responses to unrelated pathogens. HBV co-administration did not have a significant impact on responses overall but influenced the heterologous effects of neonatal BCG vaccination in a sex-differential manner. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Pittet, Laure F AU - Pittet LF AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: laure.pittet@mcri.edu.au. FAU - Cox, Lianne AU - Cox L AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: liannecox@gmail.com. FAU - Freyne, Bridget AU - Freyne B AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, College of Medicine, University of Malawi, Queen Elizabeth Central Hospital, Malawi; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool and Malawi-Liverpool Wellcome Trust Research Programme, Malawi. Electronic address: Bridget.freyne@liverpool.ac.uk. FAU - Germano, Susie AU - Germano S AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: susie.germano@mcri.edu.au. FAU - Bonnici, Rhian AU - Bonnici R AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: rhian.bonnici@mcri.edu.au. FAU - Gardiner, Kaya AU - Gardiner K AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: kaya.gardiner@rch.org.au. FAU - Donath, Susan AU - Donath S AD - Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Clinical Epidemiology & Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: susan.donath@mcri.edu.au. FAU - Collins, Clare L AU - Collins CL AD - Newborn Services, Joan Kirner Women & Children's, Sunshine Hospital, Western Health, Melbourne, Australia. Electronic address: clare.collins@wh.org.au. FAU - Casalaz, Dan AU - Casalaz D AD - Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: DCasalaz@mercy.com.au. FAU - Robins-Browne, Roy AU - Robins-Browne R AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address: r.browne@unimelb.edu.au. FAU - Flanagan, Katie L AU - Flanagan KL AD - School of Health Sciences, University of Tasmania, Hobart, Tasmania, Australia; School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia; Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia; Tasmanian Vaccine Trial Centre, Level 5, Launceston General Hospital, Launceston, Tasmania, Australia. Electronic address: katie.flanagan@ths.tas.gov.au. FAU - Messina, Nicole L AU - Messina NL AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: nicole.messina@mcri.edu.au. FAU - Curtis, Nigel AU - Curtis N AD - Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia. Electronic address: Nigel.Curtis@rch.org.au. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220131 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (BCG Vaccine) RN - 0 (Cytokines) RN - 0 (Hepatitis B Vaccines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - *BCG Vaccine MH - Cytokines MH - Female MH - *Hepatitis B Vaccines MH - Humans MH - Infant, Newborn MH - Interferon-gamma MH - Male MH - Vaccination OTO - NOTNLM OT - Bacille Calmette-Guerin (BCG), Mycobacterium bovis OT - Hepatitis B vaccine OT - Neonate OT - Prevention OT - Vaccine non-specific effect COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/02/03 06:00 MHDA- 2022/03/11 06:00 CRDT- 2022/02/02 05:31 PHST- 2021/09/25 00:00 [received] PHST- 2021/11/23 00:00 [revised] PHST- 2022/01/07 00:00 [accepted] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2022/02/02 05:31 [entrez] AID - S0264-410X(22)00020-2 [pii] AID - 10.1016/j.vaccine.2022.01.005 [doi] PST - ppublish SO - Vaccine. 2022 Feb 23;40(9):1334-1341. doi: 10.1016/j.vaccine.2022.01.005. Epub 2022 Jan 31.