Mycobacterium bovis BCG / Murdoch Children’s Research Institute - LARVOL DELTA

Neonatal BCG vaccination to prevent respiratory infections in the first 5 years of life: results from the MIS BAIR randomised controlled trial. (PubMed, Vaccine) - P3 | "In a low-mortality setting, there was not clear evidence that neonatal BCG vaccination significantly reduces the incidence of early life hospitalisation for LRTI, infections or respiratory illness. The ability to detect any effect of BCG may have been limited by the increasing missing data over the course of follow-up."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Neonatal BCG vaccination to prevent asthma: Results from the MIS BAIR randomized controlled trial. (PubMed, Pediatr Allergy Immunol) - P3 | "While the point estimates suggested BCG vaccination might protect against asthma, the wide uncertainty around the estimates means further studies with larger sample sizes are needed to evaluate the long-term benefits of BCG vaccination beyond its primary indication."

Clinical • Journal • Allergy • Asthma • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Completed | Sponsor: Murdoch Childrens Research Institute | Active, not recruiting ➔ Completed

Trial completion • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Active, not recruiting | Sponsor: Murdoch Childrens Research Institute | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2023

Trial completion date • Trial primary completion date • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

Accelerated Bacille Calmette-Guérin reactions: More than meets the eye. (PubMed, Heliyon) - "An accelerated BCG reaction occurred in 755/1984 (38 %) of BCG-vaccinees...Prior mycobacterial exposure, through prior BCG vaccination (OR 2.46, 95%CI 1.93-3.13, p < 0.001) or latent TB infection (OR 4.17, 95%CI 1.16-14.93, p = 0.03), and female sex (OR 1.27, 95%CI 1.03-1.57, p = 0.02), were key determinants for the occurrence of an accelerated BCG reaction. The development of an accelerated local reaction to BCG vaccination in an individual without prior history of BCG vaccination, should prompt consideration of further investigations for potential underlying TB infection."

Journal • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial. (PubMed, Lancet Infect Dis) - P3 | "BCG-Denmark vaccination did not reduce initial QFT Plus conversion risk in Brazilian health-care workers. This finding underscores the need to better understand tuberculosis prevention in populations at high risk."

Journal • Cardiovascular • Diabetes • Hypertension • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IFNG

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Active, not recruiting | Sponsor: Murdoch Childrens Research Institute | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis: a nested randomised controlled trial. (PubMed, EClinicalMedicine) - P3 | "Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine...BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors."

Journal • Herpes Simplex • Novel Coronavirus Disease

BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists. (PubMed, Front Immunol) - "At V2 + 28, interferon-γ and monocyte chemoattractant protein-1 responses to S. aureus, E. coli, L. monocytogenes, BCG vaccine, H. influenzae, hepatitis B antigen, poly(I:C) and R848 stimulations were decreased compared to pre-vaccination. BNT162b2 vaccination in children alters cytokine responses to heterologous stimulants, particularly one month after vaccination. This study is the first to report the immunological heterologous effects of COVID-19 vaccination in children."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases • CCL2 • IFNG • IL15 • IL17A • IL6

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Active, not recruiting | Sponsor: Murdoch Childrens Research Institute | Trial completion date: Jul 2023 ➔ Dec 2023 | Trial primary completion date: Jul 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers. (PubMed, N Engl J Med) - P3 | "Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.)."

Journal • Immune Modulation • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination. (PubMed, Heliyon) - "The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Active, not recruiting | Sponsor: Murdoch Childrens Research Institute | Trial primary completion date: Dec 2022 ➔ Jul 2023

Trial primary completion date • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

MIS BAIR: Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction (clinicaltrials.gov) - P3 | N=1272 | Active, not recruiting | Sponsor: Murdoch Childrens Research Institute | Trial completion date: Jul 2022 ➔ Jul 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Allergy • Atopic Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases

Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis. (PubMed, Lancet Glob Health) - "Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations."

Journal • Retrospective data • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IFNG

Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes. (PubMed, Sci Adv) - "This phenomenon mediates, at least in part, the beneficial off-target effects of the BCG vaccine...Genes associated with this epigenetic signature are involved in viral response pathways, consistent with the reported off-target protection against viral infections in neonates, adults, and the elderly. Our findings indicate that the off-target effects of BCG in infants are accompanied by epigenetic remodeling of circulating monocytes that lasts more than 1 year."

Epigenetic controller • Journal • Infectious Disease

BRACE: BCG Vaccination to Protect Healthcare Workers Against COVID-19 (clinicaltrials.gov) - P3 | N=6828 | Completed | Sponsor: Murdoch Childrens Research Institute | Active, not recruiting ➔ Completed | N=10078 ➔ 6828

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Bacille Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T Cell Responses in Infants. (PubMed, Am J Respir Crit Care Med) - "BCG skin reaction correlated with the magnitude of mycobacteria-specific T cell responses. As T cell responses play a key role in defence against mycobacteria, the relationship between BCG scar formation and protection against tuberculosis should be revisited. This may also extend to the need for BCG re-vaccination in scar-negative individuals."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8 • IFNG • IL13 • IL2

BRACE: BCG Vaccination to Protect Healthcare Workers Against COVID-19 (clinicaltrials.gov) - P3; N=10078; Active, not recruiting; Sponsor: Murdoch Childrens Research Institute; Trial primary completion date: Jun 2021 ➔ Nov 2021

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

BCG vaccine's off-target effects on allergic, inflammatory and autoimmune diseases: Worth another shot? (PubMed, J Allergy Clin Immunol) - No abstract available

Journal • Allergy • Immunology • Inflammation

[VIRTUAL] SCAR FORMATION FOLLOWING INFANT IMMUNISATION WITH BACILLE CALMETTE-GUÉRIN IS ASSOCIATED WITH ENHANCED MYCOBACTERIUM-SPECIFIC T-CELL RESPONSES (ESPID 2021) - " 208 infants in Australia were randomised to receive one of three BCG vaccine strains at birth (BCG-Denmark, n=53; BCG-Japan, n=55; or BCG-Russia, n=56) or at 2 months of age (BCG-Denmark, n=44)... BCG scar formation is associated with higher mycobacteria-specific T-cell responses. As T-cell responses are important in the immune response against TB, the relationship between BCG scar formation and protection against TB should be explored further."

Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • IFNG • IL2

Immunisation status of children with cerebral palsy in rural Bangladesh: results from the Bangladesh Cerebral Palsy Register (BCPR). (PubMed, Infect Disord Drug Targets) - "To the best of our knowledge, this is the first paper to use a formal CP register to examine the relationship between CP and immunisation status in a low or middle income country like Bangladesh. Our data suggest that more than two thirds of children with CP in rural Bangladesh did not receive immunisation during a recent national campaign."

Clinical • Journal • Cerebral Palsy • CNS Disorders • Infectious Disease • Pediatrics

BRACE: BCG Vaccination to Protect Healthcare Workers Against COVID-19 (clinicaltrials.gov) - P3; N=10078; Active, not recruiting; Sponsor: Murdoch Childrens Research Institute; Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The safety of BCG revaccination: A systematic review. (PubMed, Vaccine) - "Evidence to date suggests that revaccination with BCG vaccine carries minimal risk. Future studies of BCG vaccine for novel applications should report adverse event data stratified by prior BCG vaccination status."

Clinical • Journal • Review • Infectious Disease • Respiratory Diseases • Tuberculosis

BRACE: BCG Vaccination to Protect Healthcare Workers Against COVID-19 (clinicaltrials.gov) - P3; N=10078; Recruiting; Sponsor: Murdoch Childrens Research Institute; Trial primary completion date: Oct 2020 ➔ Jun 2021

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease