Hepatitis B vaccine co-administration influences the heterologous effects of neonatal BCG vaccination in a sex-differential manner

Laure F Pittet; Lianne Cox; Bridget Freyne; Susie Germano; Rhian Bonnici; Kaya Gardiner; Susan Donath; Clare L Collins; Dan Casalaz; Roy Robins-Browne; Katie L Flanagan; Nicole L Messina; Nigel Curtis

doi:10.1016/j.vaccine.2022.01.005

Hepatitis B vaccine co-administration influences the heterologous effects of neonatal BCG vaccination in a sex-differential manner

Vaccine. 2022 Feb 23;40(9):1334-1341. doi: 10.1016/j.vaccine.2022.01.005. Epub 2022 Jan 31.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: susie.germano@mcri.edu.au.
⁵ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: rhian.bonnici@mcri.edu.au.
⁶ 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.
⁷ 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.
⁸ Newborn Services, Joan Kirner Women & Children's, Sunshine Hospital, Western Health, Melbourne, Australia. Electronic address: clare.collins@wh.org.au.
⁹ Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: DCasalaz@mercy.com.au.
¹⁰ 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.
¹¹ 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.
¹² 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.
¹³ 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.

PMID: 35105495
DOI: 10.1016/j.vaccine.2022.01.005

Abstract

Introduction: Bacille Calmette-Guérin (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-γ), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-α) responses was analysed using linear regression.

Results: Overall, BCG vaccination alone or with HBV co-administration reduced IFN-γ and MCP-1 responses to heterologous stimulants. HBV vaccination alone did not alter heterologous cytokine responses. In general, males produced more IFN-γ and TNF-α 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-γ and MCP-1 responses. In contrast, compared with females in the No vaccine group, females in the BCG group had higher IFN-γ 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.

Keywords: Bacille Calmette-Guérin (BCG), Mycobacterium bovis; Hepatitis B vaccine; Neonate; Prevention; Vaccine non-specific effect.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

BCG Vaccine*
Cytokines
Female
Hepatitis B Vaccines*
Humans
Infant, Newborn
Interferon-gamma
Male
Vaccination

Substances

BCG Vaccine
Cytokines
Hepatitis B Vaccines
Interferon-gamma