MIS BAIR – Melbourne Infant Study: BCG for Allergy and Infection Reduction
- Project status: Active
Research area: Infection, Immunity and Global Health > Infectious Diseases
Can Bacille Calmette-Guérin (BCG) vaccination influence the development of an infant’s immune system so that it’s better at fighting infections and is less prone to allergy?
Since 2015, this study has been investigating whether a 100-year-old vaccine developed to prevent tuberculosis, BCG vaccine, could also help reduce allergies, eczema, infections and asthma in infants and children.
Since 2015, this study has been investigating whether a 100-year-old vaccine developed to prevent tuberculosis, BCG vaccine, could also help reduce allergies, eczema, infections and asthma in infants and children.
Overview
Since 2015, this study has been investigating whether a 100-year-old vaccine developed to prevent tuberculosis, called Bacille Calmette-Guérin (BCG) vaccine, could also help reduce allergies, eczema, infections and asthma in infants and children.
Why is this research important?
Allergies
One in 10 Melbourne infants develop a food allergy by 12 months of age.
Eczema
Almost a third of babies suffer from eczema before their first birthday.
Chest infection
Nearly half of infants will have a chest infection in the first year of life.
Asthma
Around 10 percent of children under 14 have asthma as a long-term condition.
What is the MIS BAIR study?
Investigating the immune boosting effects of BCG vaccine in Australian children, led by Professor Nigel Curtis.
Until the 1980s, Bacille Calmette-Guérin (BCG) vaccine was given to Australian children to prevent tuberculosis (TB). Routine administration was discontinued because of the country’s low prevalence of TB.
However, BCG is still administered to over 120 million infants worldwide each year. In high-mortality countries, neonatal BCG vaccination is associated with a halving in mortality in the first year of life. Research also shows the 100-year-old vaccine boosts immunity to protect against respiratory viral infections.
To find out more, in 2015, the Murdoch Children’s Research Institute launched the MIS BAIR trial led by Chief Investigator Professor Nigel Curtis. The global study team is exploring the immune boosting effects of BCG in Melbourne children and whether this vaccine can reduce the risk of diseases such as food allergy, eczema and asthma.
Ultimately, by understanding the 'off-target' effects of BCG vaccine, the study could change the trajectory of children’s health and contribute to decreased childhood allergies and infections.
MIS BAIR part one
Funded by the National Health and Medical Research Council (NHMRC), the MIS BAIR randomised controlled trial recruited over 1200 babies with half receiving the BCG vaccine within 10 days of birth. Investigators studied differences between the two groups during the first year of life, looking for the causes and signs of food allergy, eczema and infections.
MIS BAIR part two
Thanks to additional funding from the National Health and Medical Research Council (NHMRC), part two of the study extends the original MIS BAIR project. The study team has continued to compare children in the original two groups until age five, looking at the same clinical outcomes with the addition of asthma.
How common is childhood allergy in Australia?
Allergic diseases have risen dramatically over the past few decades in Australia. In fact, we now have the highest documented rates worldwide.
- Almost a third of babies have suffered from eczema by 12 months of age.
- One in 10 will have an allergy to at least one food at one year of age.
- One in 10 Australians suffer from asthma.
What is the BCG vaccine?
BCG vaccine is used to prevent tuberculosis (TB). Given at birth, it is one of the oldest, most widely used and well-tolerated vaccines.
The vaccine is routinely given to babies in many developed countries, including Ireland and some parts of the UK and Europe. This vaccine is no longer routinely given in Australia, as we are fortunate to have very low rates of TB.
Can BCG reduce allergy and infection?
BCG vaccine has been found to have beneficial effects on the immune system over and above its protective effect against TB.
Studies suggest the vaccine may help prevent infection as well as reduce allergic diseases such as eczema, food allergy, hay fever and asthma.
MIS BAIR five-year visits have now closed
Information for participants
What was assessed at the five-year visit?
- Weight, height, blood pressure
- Food intake
- Any allergies
- Any eczema
What tests were planned at the five-year visit?
- Skin prick test (SPT) for allergies
- Blood test (optional)
- Dental examination (optional)
- Cardiovascular assessment (optional)
Will there be a skin prick test (SPT)?
Yes. The SPT at the five-year visit was very similar to the one-year SPT. It involved placing a small amount of a food or environmental allergen, which most commonly cause allergic reactions, under the skin on the back with a small lancet. If the skin reacts, it is a good predictor of sensitisation to that substance.
If the skin prick test was positive to a food allergen at five-years of age, a food challenge test may be arranged at a later date, where your child will eat some of the food under observation in a safe environment.
If your child has a food allergy, we will arrange advice on treatment, diet and management for you.
How long did the five-year visit take?
Between 1.5 and 2 hours for this visit including the optional assessments.
Optional assessments
Blood test
If you and your child consent, we will draw a small blood sample. We will apply some numbing cream, which makes the blood test less painful. This blood sample helps the study team look at how well immune cells in the blood fight against microbes.
Dental examination
At the five-year visit, you can take part in an additional dental examination to assess bacteria in the mouth that causes tooth decay.
Tooth decay is the most common childhood disease, affecting almost half of Australian children. Bacteria in the mouth also contribute to cardiovascular diseases, which affect half of the adult Australian population.
Interestingly, healthy teeth have been linked with healthy hearts and it is emerging that oral and heart health are tightly linked.
In studying the relationship between bacteria, and oral and heart health in children, we hope to discover ways to detect - and ultimately prevent - diseases of the mouth and heart.
During the dental assessment, we will collect dental plaque using a small swab and make a 3D scan of your child’s teeth. This is very well tolerated and will only take 10 to 15 minutes. You will receive a 3D scan and dental report following your child’s examination and will have access to non-urgent dental advice via phone.
Cardiovascular assessment
There is also an opportunity for your child to take part in a cardiovascular assessment, where researchers are looking at the structure and function of the blood vessels to assess cardiovascular health.
Cardiovascular disease, such as heart attack and stroke, generally happens in adults, but we know the changes in the blood vessels that lead to cardiovascular disease develop slowly throughout childhood and into adulthood. This hardening of the arteries, also known as atherosclerosis, is caused by inflammation of the artery wall.
The BCG vaccine is known to be protective against infections, with some studies suggesting it may also reduce inflammation.
To learn more, an ultrasound of your child’s neck and abdomen will look at the blood vessels. We will also take a photo of your child’s retina (back of the eye) and ask for a urine sample.
We want to compare the health of blood vessels of children who have been given the BCG vaccine versus those who have not received the vaccine.
ICYMI: MIS BAIR Webinar with Professor Nigel Curtis and leaders of the study team (January 2021)
Participant newsletters
Participant newsletter, December 2020539.80 KB- Participant newsletter, November 2021323.19 KB
- Participant newsletter, September 2023242.30 KB
Collaborators
Thank you to our supporters.
The MIS BAIR trial is backed by the Murdoch Children’s Research Institute, Royal Children’s Hospital, The University of Melbourne, National Health and Medical Research Council, Mercy Health, Meyer Foundation, European Society for Paediatric Infectious Diseases, Swiss National Science Foundation, Nossal Institute for Global Health and the Aranday Foundation.
Messina N L, Gardiner K, Pittet L F, et al. Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology, 2024 Jul 14; doi.org/10.1111/cea.14537
Messina NL, Wang M, Forbes EK, et al. The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum. BMC Immunol. 2024 Apr 30; 25(1):24. doi: 10.1186/s12865-024-00611-5. PMID: 38689233; PMCID: PMC11059926.
Zimmermann P, Pittet LF, Jakob W, et al. The Effect of Bacille Calmette-Guérin Vaccination on the Composition of the Intestinal Microbiome in Neonates From the MIS BAIR Trial. Pediatr Infect Dis J. 2024 Apr 1; 43(4):p 378-389, April 2024. doi: 10.1097/INF.0000000000004223.PMID: 38145402.
Samantha Bannister et al., Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes. Sci. Adv. 8, eabn4002(2022). doi:10.1126/sciadv.abn4002
Leo S, Cetiner OF, Pittet LF, Messina NL, Jakob W, Falquet L, Curtis N and Zimmermann P (2023), The association between the composition of the early-life intestinal microbiome and eczema in the first year of life. Front. Microbiomes 2:1147082. doi: 10.3389/frmbi.2023.1147082
Pittet, LF, Messina, NL, Gardiner, K, et al. Prevention of infant eczema by neonatal Bacillus Calmette-Guérin vaccination: The MIS BAIR randomized controlled trial. Allergy. 2022; 77: 956–965. doi: 10.1111/all.15022
Messina NL, Pittet LF, Gardiner K, Freyne B, Francis KL, Zufferey C, Abruzzo V, Morrison C, Allen KJ, Flanagan KL, Ponsonby AL, Robins-Browne R, Shann F, South M, Vuillermin P, Donath S, Casalaz D, Curtis N. Neonatal Bacille Calmette-Guérin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial. J Infect Dis. 2021 Oct 13;224(7):1115-1127. doi: 10.1093/infdis/jiab306. PMID: 34146093. doi: 10.1093/infdis/jiab306
Bridget Freyne et al., Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial, The Journal of Infectious Diseases, Volume 221, Issue 12, 15 June 2020, Pages 1999–2009, doi: 10.1093/infdis/jiaa030
Noé A, Dang TD, Axelrad C, Burrell E, Germano S, Elia S, Burgner D, Perrett KP, Curtis N and Messina NL (2023) BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists. Front. Immunol. 14:1242380. doi: 10.3389/fimmu.2023.1242380
Contact us
MIS BAIR trial
Murdoch Children's Research Institute
The Royal Children's Hospital
50 Flemington Road
Parkville VIC 3052
Australia
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Prevention of infant eczema by neonatal BCG vaccination-the MIS BAIR randomised controlled trial
Hear from Dr Laure Pittet, a paediatrician at the Murdoch Children’s Research Institute and The University of the Melbourne, as she discusses early MIS BAIR findings. Laure explains how the MIS BAIR trial found that neonatal BCG vaccination reduces the risk of eczema at 12 months of age, particularly in high-risk infants.
Hear from Dr Laure Pittet, a paediatrician at the Murdoch Children’s Research Institute and The University of the Melbourne, as she discusses early MIS BAIR findings. Laure explains how the MIS BAIR trial found that neonatal BCG vaccination reduces...
Hear from Dr Laure Pittet, a paediatrician at the Murdoch Children’s Research Institute and The University of the Melbourne, as she discusses early MIS BAIR findings. Laure explains how the MIS BAIR trial found that neonatal BCG vaccination reduces the risk of eczema at 12 months of age, particularly in high-risk infants.
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