Long-term non-specific effects of BCG and smallpox vaccinations
Evidence indicates that live attenuated vaccines reduce morbidity and mortality to an extent that is not only due to the protection against the target disease of the vaccine. Most of the research involves children, and the potential long-term effects among adults are less explored. This PhD project aims to explore the long-term non-specific effects of the vaccines against smallpox (vaccinia) and against tuberculosis (BCG) on adult health. This will be done in five studies with mortality, infections, and cancer (malignant melanoma) as main outcomes. If early exposure to certain vaccines changes ones probability of non-related infectious diseases and general survival, evaluators of vaccine programs should consider these aspects too.
The question about whether vaccines may have a protective effect against diseases that they were not intended to prevent against is more relevant now than ever.
The topic has been debated for decades but last year the World Health Organization (WHO) stated that epidemiological studies indicate that some vaccines are associated with strong reductions in child mortality than can be explained by the prevention of the target diseases. WHO officially warrants further research on the non-specific effects of vaccines.
Most vaccine research focuses on disease-specific outcomes and not the effects on overall levels of morbidity and mortality (the non-specific effects). Research on the non-specific effects was initiated in Guinea-Bissau but studies from other countries are now emerging. The overall pattern observed is that the live attenuated vaccines such as the vaccines against smallpox (vaccinia), tuberculosis (BCG), measles, and polio (oral polio vaccine) are associated with protection against a broad range of unrelated infections. For BCG it has been shown that it trains the immune system through epigenetic changes to be more resistant to unrelated infections. The effects are generally stronger in females than in males, for reasons we still do not understand.
Stakeholders in global health (United Nations, Red Cross, Bill and Melinda Gates Foundation) have set goals to eradicate measles, rubella, and polio within decades. This is an ambitious and honourable public health goal. However if the live attenuated vaccines against these diseases have beneficial non-specific effects it may become a problem if the diseases are eradicated and the corresponding vaccines are phased out: Paradoxically morbidity and mortality may increase because individuals are no longer exposed to the beneficial non-specific effects of these vaccines.
There is therefore an urgent need to understand the non-specific effects of vaccines. The vast majority of studies have examined the short-term non-specific effects for childhood morbidity and mortality but there is little knowledge about the potential long-term effects vaccines. The PhD project will considerably increase the amount of research on the long-term non-specific effects of vaccines in adult life by conducting five epidemiological studies of vaccinia and BCG on mortality, infectious diseases, and cancer (malignant melanoma).
Description of the cohort
The study population of the studies I-III is Danish individuals who went to school in the municipality of Copenhagen during the phase out of BCG and smallpox vaccination. For study IV the study population is all women from rural Guinea-Bissau, for study V individuals from urban Guinea-Bissau.
Data and biological material
The studies I-III based on data from Denmark use the Copenhagen School Health Record Register, The Danish Civil Registration System, The Danish Register of Causes of Death, the Danish Cancer Register, The Danish National Patient Register.
The studies IV-V based on data from Guinea-Bissau uses survey data collected by the Bandim Health Project
Collaborating researchers and departments
OPEN Odense Patient data Explorative Network, Odense University Hospital
- Associate Professor and Principal supervisor, Henrik Ravn, PhD
- Professor Christine Stabell Benn, MD, PhD, DMSc
Bandim Health Project, Statens Serum Institut
- Co-Supervisors Signe Sørup, PhD
- Co-Supervisor Ane Bærent Fisker, MD, PhD
- Co-Supervisor Peter Aaby, DMSc
- Andreas Andersen, PhD
Institute of Preventive Medicine, Frederiksberg Hospital
- Associate Professor Jennifer Baker, PhD
- Kathrine Damm Meyle, MD
- Line Hougaard, MD