Nelly Amenyogbe
Honorary Research Associate
BSc PhD
nelly.amenyogbe@thekids.org.au
Dr. Amenyogbe’s research interests centre around the concept of host resilience. Simply put, the paradigm that the outcome of an infection, or the response to a vaccination depends not only on the infectious microbe or type of vaccine, but on the immune fitness of the host that receives it. With this, the translational focus of her research program is to improve host immune fitness to increase resilience to a wide range of potential infections at once. Her focus is on vulnerable populations that disproportionately suffer from infectious death. Specifically, this includes pregnancy and the newborn period, and in low-income settings where vulnerable populations are most likely to suffer from infectious disease.
To accomplish this, Amenyogbe uses animal models combined with mining big data from human studies. Her program aims to better understand how our microbial environment, or gut microbiome, impacts on our immune fitness. Her previous work identified correlations between the gut microbiome and systemic immunity in children around the world that may hold the clue to improve outcome of infection or vaccination.
Her research also includes the non-specific, or pathogen-agnostic effects of vaccines. This involves understanding broad effects that vaccines have on host immunity unrelated to their impact on pathogen-specific immunity. For example, Amenyogbe’s previous research showed how BCG, the vaccine against tuberculosis, reduces risk to die from newborn sepsis within days of being given.
Education and Qualifications
- BSc, Microbiology & Immunology, University of British Columbia
- PhD, Experimental Medicine, University of British Columbia
Active Collaborations
- Newborn vaccine responsiveness with The Expanded Program for Immunization Consortium
- Non-specific effects of vaccines with the Bandim Health Project
- Newborn-maternal microbiome with the Kintampo Health Research Centre
Published research
The mark of success: The role of vaccine-induced skin scar formation for BCG and smallpox vaccine-associated clinical benefits
Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential.
BCG-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.
Implications 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.
Off-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).
Ontogeny 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.
Bacterial 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.
Immunisation 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.
A 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.
Biogeography 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.
Multi-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.
Systems 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.
Innate 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.
BCG 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
Maternal 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
Clinical 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
Dynamic molecular changes during the first week of human life follow a robust developmental trajectory
Systems biology and innovative data integration can provide fresh insights into the molecular ontogeny of the first week of life