Honorary Research Associate
PhD, M.D., SFUW
Professor Tobias Kollmann is a paediatric infectious diseases physician with a deep passion for making an impact at the convergence of clinical care and fundamental research. He is currently an Honorary Research Associate with the Immunology and Breast Feeding at Telethon Kids Institute.
Professor Kollmann completed both his MD and PhD at the Albert Einstein College of Medicine, New York, USA. He then conducted his Residency and Fellowship at the University of Washington, Seattle, USA, before joining the Paediatric Infectious Disease Division at the University of British Columbia (UBC), Canada in 2005.
Professor Kollmann also is the Director of both The Precision Health Accelerator that provides complete end-to-end solutions enabling parallel multi-omic analysis, and of The Virtual Academy that brings together the world’s leading life science and data science experts.
As a member of the WHO Expert Advisory Group on Non-specific Immunological Effects of Vaccination committee, Professor Kollmann is international leader in vaccinology. He is a member on multiple NIH Review panels associated with the National Institute of Allergy and Infectious Disease (NIAID) including Human Immunology Project Consortium, Centres of Excellence in Translational Research and Cooperative Centres on Human Immunology.
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Publications
April 2023
Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers
The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019.
Published research Immunisation Influenza Infectious Diseases Vaccine Trials Group Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Subsite: Walyan COVID-19 Immunology and Breast Feeding Strep A & ARF TherapeuticsJuly 2023Interferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial
Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission.
Published research Infectious Diseases Airway Epithelial Research P4 Respiratory Health for Kids Subsite: Walyan Systems Vaccinology COVID-19May 2023BCG-Induced Immune Training: Interplay between Trained Immunity and Emergency Granulopoiesis
Bacille Calmette-Guérin (BCG) is the most commonly administered vaccine in human history. The medical application of BCG extends far beyond the fight against tuberculosis. Despite its stellar medical record over 100 years, insight into how BCG provides this vast range of benefits is largely limited, both for its pathogen-specific (tuberculosis) as well as pathogen-agnostic (other infections, autoimmunity, allergies, and cancer) effects.
Asthma Published research Infectious Diseases Systems Vaccinology Allergy TuberculosisMay 2023Defining the pediatric response to SARS-CoV-2 variants
The global population has been severely affected by the coronavirus disease 2019 (COVID-19) pandemic, however, with older age identified as a risk factor, children have been underprioritized. This article discusses the factors contributing to the less severe response observed in children following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including, differing viral entry receptor expression and immune responses.
Published research Early Childhood Development Infectious Diseases Infectious Diseases Epidemiology Airway Epithelial Research P4 Respiratory Health for Kids Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Healthy Skin and ARF Prevention Subsite: Walyan Systems Vaccinology COVID-19 Child and adolescent healthJuly 2023Maternal Vaccination to Prevent Adverse Pregnancy Outcomes: An Underutilized Molecular Immunological Intervention?
Adverse pregnancy outcomes including maternal mortality, stillbirth, preterm birth, intrauterine growth restriction cause millions of deaths each year. More effective interventions are urgently needed. Maternal immunization could be one such intervention protecting the mother and newborn from infection through its pathogen-specific effects.
Published research Immunisation Systems Vaccinology Maternal healthApril 2023The non-specific effects of maternal immunization on birth outcomes: The evidence, mechanisms, and the implications
Preterm birth (PTB) and stillbirth remain two of the most important causes of death, morbidity, and disability in childhood. Despite efforts to reduce PTB and stillbirth worldwide, rates of these adverse outcomes remain persistently elevated, independent of income setting. There is an urgent need for more effective interventions to reduce associated neonatal and early childhood morbidity and mortality.
Published research Early Childhood Development Immunisation Systems Vaccinology Pre-term birth Child disabilityMay 2023Implications of Non-Specific Effects for Testing, Approving, and Regulating Vaccines
The current framework for testing and regulating vaccines was established before the realization that vaccines, in addition to their effect against the vaccine-specific disease, may also have "non-specific effects" affecting the risk of unrelated diseases. Accumulating evidence from epidemiological studies shows that vaccines in some situations can affect all-cause mortality and morbidity in ways that are not explained by the prevention of the vaccine-targeted disease.
Published research Immunisation Systems VaccinologyNovember 2022The Troublesome Ticks Research Protocol: Developing a Comprehensive, Multidiscipline Research Plan for Investigating Human Tick-Associated Disease in Australia
In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia.
Published research Systems VaccinologyApril 2022Off-target effects of bacillus Calmette-Guerin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19
Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette-Guérin vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19).
Published research Immunisation Human Development and Community Wellbeing Systems Immunology Infectious Disease Implementation Research Vaccine Trials Group Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases COVID-19 Immune system Strep A & ARF TherapeuticsNovember 2022A systems biology approach to better understand human tick-borne diseases
Tick-borne diseases are a growing global health concern. Despite extensive studies, ill-defined tick-associated pathologies remain with unknown aetiologies. Human immunological responses after tick bite, and inter-individual variations of immune-response phenotypes, are not well characterised.
Published research Infectious Diseases Neonatal Health Systems VaccinologyOctober 2022FastMix: a versatile data integration pipeline for cell type-specific biomarker inference
Flow cytometry (FCM) and transcription profiling are the two widely used assays in translational immunology research. However, there is no data integration pipeline for analyzing these two types of assays together with experiment variables for biomarker inference.
Published research Systems VaccinologyAugust 2022Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells
Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate.
Published research Airway Epithelial Research Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Healthy Skin and ARF Prevention Clinical Epigenetics Subsite: Walyan Systems Vaccinology COVID-19 Respiratory viral infectionsJune 2022The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines
With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination.
Published research Immunisation Influenza Infectious Diseases Vaccine Trials Group Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Systems VaccinologyMay 2022Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro
Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms.
Published research Immunisation Systems VaccinologyFebruary 2022Cutaneous CpG adjuvant conditioning to enhance vaccine responses
Adjuvant activity of the Toll receptor 9 agonist CpG 1826 was compared when given subcutaneously (s.c.) together with ovalbumin (s.c.[CpG + Ova]), or when given by either s.c. or intradermally (i.d.) routes two days prior to s.c. ovalbumin.
Published research Immunisation Systems VaccinologyJanuary 2022Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy
The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy.
Published research Immunisation Vaccine Trials Group Systems VaccinologyOctober 2021Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response
Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy.
Published research Immunisation Infectious Diseases Systems VaccinologyOctober 2021BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)
BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.
Published research Immunisation Influenza Ear Health COVID-19October 2021Lactiplantibacillus plantarum–Nomad and Ideal Probiotic
Probiotics are increasingly recognized as capable of positively modulating several aspects of human health. There are numerous attributes that make an ideal probiotic. Lactiplantibacillus plantarum (Lp) exhibits an ecological and metabolic flexibility that allows it to thrive in a variety of environments.
Published research Systems VaccinologySeptember 2021Ontogeny of plasma cytokine and chemokine concentrations across the first week of human life
Early life is marked by distinct and rapidly evolving immunity and increased susceptibility to infection. The vulnerability of the newborn reflects development of a complex immune system in the face of rapidly changing demands during the transition to extra-uterine life.
Published research Early Childhood Development Systems Vaccinology Immune systemSeptember 2021Searching for a technology-driven acute rheumatic fever test: the START study protocol
The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus.
Published research Rheumatic Heart Disease Systems Immunology Group A Streptococcal & Rheumatic Heart Disease Computational Biology Systems VaccinologyAugust 2021A cluster randomized trial of interferon ss-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19)
SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19).
Infectious Diseases Subsite: Walyan Systems Vaccinology COVID-19July 2021Bacterial and Fungal Gut Community Dynamics Over the First 5 Years of Life in Predominantly Rural Communities in Ghana
Bacterial and fungal microbiotas are increasingly recognized as important in health and disease starting early in life. However, microbiota composition has not yet been investigated in most rural, low-resource settings, and in such settings, bacterial and fungal microbiotas have not been compared.
Published research Systems VaccinologyJuly 2021Immunological mechanisms of vaccine-induced protection against COVID-19 in humans
Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. Several vaccines, including mRNA, adenoviral-vectored, protein subunit and whole-cell inactivated virus vaccines, have now reported efficacy in phase III trials and have received emergency approval in many countries.
Published research Infectious Diseases Systems Vaccinology COVID-19May 2021Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life
Human adenosine deaminases (ADAs) modulate the immune response: ADA1 via metabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults.
Published research Early Childhood Development Systems VaccinologyApril 2021Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings.
Published research Immunisation Infectious Diseases Systems VaccinologyApril 2021A place for neutrophils in the beneficial pathogen-agnostic effects of the BCG vaccine
The BCG vaccine has long been recognized for reducing the risk to suffer from infectious diseases unrelated to its target disease, tuberculosis. Evidence from human trials demonstrate substantial reductions in all-cause mortality, especially in the first week of life. Observational studies have identified an association between BCG vaccination and reduced risk of respiratory infectious disease and clinical malaria later in childhood.
Published research Immunisation Infectious Diseases Systems VaccinologyApril 2021One vaccine for life: Lessons from immune ontogeny
There remains a general misconception that the immune status of the fetus and neonate is immature or insufficient. However, emerging research in immune ontogeny prompts reconsideration of this orthodoxy, reframing this period instead as one of unique opportunity. Vaccine responses (qualitative and quantitative) vary between individuals, and across demographic cohorts. Elements of baseline immune status and function predict vaccine response - some of these factors are well described, others remain a subject of ongoing research, especially with the rapidly expanding field of 'omics' research, enabled by development of highly granular immune profiling techniques and increasing computational capacity.
Published research Immunisation Infectious Diseases Systems VaccinologyJanuary 2021The Fifth International Neonatal and Maternal Immunization Symposium (INMIS 2019): Securing Protection for the Next Generation
Despite significant progress in reaching some milestones of the United Nations Sustainable Development Goals, neonatal and early infant morbidity and mortality remain high, and maternal health remains suboptimal in many countries. Novel and improved preventative strategies with the potential to benefit pregnant women and their infants are needed, with maternal and neonatal immunization representing effective approaches.
Published research Immunisation Systems VaccinologyJanuary 2021Biogeography of the Relationship between the Child Gut Microbiome and Innate Immune System
The gut microbiome is a well-recognized modulator of host immunity, and its compositions differ between geographically separated human populations. Systemic innate immune responses to microbial derivatives also differ between geographically distinct human populations. However, the potential role of the microbiome in mediating geographically varied immune responses is unexplored. We here applied 16S amplicon sequencing to profile the stool microbiome and, in parallel, measured whole-blood innate immune cytokine responses to several pattern recognition receptor (PRR) agonists among 2-year-old children across biogeographically diverse settings. Microbiomes differed mainly between high- and low-resource environments and were not strongly associated with other demographic factors. We found strong correlations between responses to Toll-like receptor 2 (TLR2) and relative abundances of Bacteroides and Prevotella populations, shared among Canadian and Ecuadorean children.
Published research Systems VaccinologyNovember 2020Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort
Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.
Published research Immunisation Infectious Diseases Systems VaccinologyNovember 2020Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults
Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling.
Published research Infectious Diseases Systems VaccinologyNovember 2020Innate Immune Responses and Gut Microbiomes Distinguish HIV-Exposed from HIV-Unexposed Children in a Population-Specific Manner
In both high- and low-income countries, HIV-negative children born to HIV-positive mothers (HIV exposed, uninfected [HEU]) are more susceptible to severe infection than HIV-unexposed, uninfected (HUU) children, with altered innate immunity hypothesized to be a cause. Both the gut microbiome and systemic innate immunity differ across biogeographically distinct settings, and the two are known to influence each other.
Published research Systems VaccinologyMay 2020The non-specific and sex-differential effects of vaccines
The textbook view of vaccination is that it functions to induce immune memory of the specific pathogen components of the vaccine, leading to a quantitatively and qualitatively better response if the host is exposed to infection with the same pathogen
Published research Immunisation Systems VaccinologyJune 2020Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome?
Baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses
Published research Immunisation Infectious Diseases Systems VaccinologyMay 2020Interferon-α2b Treatment for COVID-19
We describe here the effects of treatment with interferon-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China
Published research Infectious Diseases Systems VaccinologyMay 2020Vaccination strategies to enhance immunity in neonates
Protection may be further improved by integrating these approaches, namely vaccinating the neonate under the cover of vertically transferred maternal immunity
Published research Immunisation Infectious Diseases Systems VaccinologyMay 2020BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis
We found that BCG, in a mouse model of neonatal polymicrobial sepsis, induced granulocyte colony-stimulating factor (G-CSF) within hours of administration
Published research Infectious Diseases Systems VaccinologyMay 2020Maternal HIV infection alters antimicrobial immunity in exposed and uninfected infants
Implementation of lifelong ART of all HIV-infected women has the potential to improve maternal determinants of protective immunity in the young infant
Published research Infectious Diseases Systems VaccinologyApril 2020Clinical protocol for a longitudinal cohort study to identify markers of vaccine immunogenicity in newborn infants in the gambia and papua New Guinea
Immunity is distinct in early life and greater precision is required in our understanding of mechanisms of early life protection to inform development of new pediatric vaccines
Published research Immunisation Infectious Diseases Vaccine Trials Group Systems VaccinologyOctober 2019Malt1 deficient mice develop osteoporosis independent of osteoclast-intrinsic effects of Malt1 deficiency
Malt1 deficient mice develop an osteoporotic phenotype with increased osteoclastogenesis in vivo, but suggest that this is caused by inflammation
Published research Systems Vaccinology -
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