A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study

NCT02444611 | Completed DMC

• 1 other identifier: VAC/01 ELVIS
• Study Type: interventional
• Target: 185
• Locations: 1 country
• Sites: 1

Brief Summary

Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood disease-specific immunisation is irrefutably linked to the decline in deaths from these targeted infections over the last century. However, neonatal immunisation is limited, in part, by the impaired adaptive immune function in this age group. There is now an expanding body of evidence for heterologous ('non-specific') effects of various vaccines used in childhood. This refers to the immunomodulatory capabilities of vaccines to influence immune outcomes beyond the vaccine's specific targeted disease. The underlying immunological mechanisms responsible for these effects are incompletely understood, but evidence is mounting that the innate immune system is central to these observed effects. This study is a randomised controlled trial designed to determine the influence of two commonly administered neonatal immunisations, BCG and Hepatitis B vaccine, given at birth, on the neonatal immune responses to non-specific antigens. The investigators will recruit 200 newborns at the Mercy Hospital for Women in Melbourne, Australia over a 1-year period. These babies will be allocated randomly to one of 4 groups, receiving these 2 vaccines in different combinations, at 2 set time points. (at birth and 1 week post randomisation) A blood sample will be taken at 1-week post randomisation for in vitro immunological analyses. This study will improve current understanding of the influence of vaccines on neonatal immunity and will help develop strategies exploiting beneficial heterologous ('non-specific') effects to improve protection against infection in the very young.

Conditions

Innate Immune Response

Keywords

neonates; BCG; Hepatitis B vaccine; vaccines; immunity; immune response; Bacille- Calmette-Guerin

Outcome Measures

Primary Outcomes (1)

• Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens

  Four hours after blood samples are collected, they will be stimulated with different concentrations of infective antigens for 20hrs. (eg killed S.aureus, S. pneumoniae, E. Coli, Haemophilus Influenza B, Group B streptococcus, C. albicans), BCG, Hepatitis B sAg). Cytokine expression will be analysed in supernatants by Luminex -based multiplex assays. The cytokines that will be measured: Interleukin-1 beta, Interleukin-1ra, Interleukin-6, Interleukin-8, Macrophage/Monocyte Chemoattractant Protein-1(MCP-1), Macrophage Inflammatory Protein (MIP) -1 alpha, MIP-1 beta, Interferon(IFN) gamma, Interleukin-10, Macrophage migration inhibitory factor (MIF), Monokine induced by interferon (MIG), Tumour necrosis factor (TNF) alpha

  7 (+-4) days post randomisation

Study Arms (4)

Group 1

ACTIVE COMPARATOR

BCG vaccine, 0,05ml intradermally at birth

Drug: BCG Vaccine

Group 2

ACTIVE COMPARATOR

BCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Drug: BCG Vaccine; Drug: Hepatitis B Vaccine

Group 3

ACTIVE COMPARATOR

Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Drug: Hepatitis B Vaccine

Group 4

NO INTERVENTION

No birth vaccines

Interventions

BCG Vaccine DRUG

intradermal vaccination

Also known as: BCG vaccine- Denmark strain, BCG Denmark, Statens Serum institute BCG vaccine, Mycobacterium bovis BCG vaccine, Danish strain, 1331, Bacillus-Calmette-Guerin

Group 1; Group 2

Hepatitis B Vaccine DRUG

intramuscular vaccination

Also known as: HB-Vax-II

Group 2; Group 3

Eligibility Criteria

• Age: Up to 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• English speaking parent
• Planned travel to a TB (Tuberculosis) endemic country within the infant's first 5 years of life
• An informed consent form must be signed and dated by the infant's mother after the nature of the study has been explained and prior to any study assessments/procedures
• The infant's mother has screened negative for HIV during this pregnancy
• The infant's mother has screened negative for Hepatitis B during this pregnancy
• There is no known household contact infected with Hepatitis B
• Born no earlier than eight weeks before estimated date of delivery
• Birth weight \>1500g
• Delivered vaginally
• Singleton pregnancy

You may not qualify if:

• Known or suspected HIV infection
• Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor---alpha (TNF---alpha) (e.g. infliximab, etanercept, adalimumab).
• Born to a mother treated with bDMARDs (biological Disease- Modifying Anti-Rheumatic drugs) (e.g. TNF---alpha blocking monoclonal antibodies) in the 3rd trimester
• Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway
• Malignancies involving bone marrow or lymphoid systems
• Serious underlying illness including severe malnutrition
• Medically unstable
• Generalised septic skin disease and skin conditions such as eczema, dermatitis and psoriasis
• Significant febrile illness
• Also excluded are infants with:
• A mother who is immunosuppressed;
• A mother who has received Intravenous immunoglobulins during her pregnancy
• A family history of immunodeficiency;
• Consanguineous parents.
• Mother who is having a planned Caesarean Section

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Royal Children's Hospital: collaborator
• Mercy Hospital for Women, Australia: collaborator

Study Sites (1)

Mercy Hospital for Women

Heidelberg, Victoria, 3084, Australia

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

BCG Vaccine; Hepatitis B Vaccines; HB-VAX

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nigel Curtis, MBBS,PHD

  Royal Children's Hospital

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: April 6, 2015
• First Posted: May 14, 2015
• Study Start: March 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 31, 2017

Record last verified: 2017-08

Locations

AU (1)