Inaugural Lecture | Qiushui He

My research interests focus on the respiratory bacterial pathogens, human immunity and genetic susceptibility to infectious diseases. We study cell-mediated and antibody responses after pertussis vaccinations and infections, and impact of gut microbiome on vaccine responses in children and adults; we study why some children are more often to have respiratory infections and asthma and some not, and the impact of genetic variations in innate immune genes. As our laboratory serves as the Finnish national reference laboratory for pertussis and diphtheria, we study changes in Bordetella pertussis and Corynebacterium diphtheriae at both genome and protein levels. We are also developing novel point of care tests for diagnosis of pertussis and other bacterial infections. The research group includes researchers from University of Turku and pediatricians from the Turku University Hospital. Since 2005 the research group has been leading two European networks EUpertstrain and EUPert-LabNet. Our research group also belongs to the newly funded University of Turku Flagship programme “InFLAMES” by Academy of Finland. Now I will briefly summarize what we have done and what we are doing about pertussis research.

Pertussis (also known as whooping cough, in Finnish “hinkuyskä”) is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis and is responsible for an estimated 160,700 deaths each year worldwide. Most of deaths occur in infants too young to be completely vaccinated. Bordetella pertussis produces many toxins and adhesins which allow the bacterium to bind to ciliated epithelial cells in human upper respiratory tract and interfere with host clearance mechanisms.

Typical symptoms of pertussis include paroxysmal cough with characteristic whooping and vomiting. Severe complications and deaths occur mostly in infants. Pertussis is often considered a childhood disease, but adults can also contract it.

Vaccination against pertussis started with whole-cell vaccines in the 1950-60s. Currently, whole-cell vaccines have been replaced by acellular vaccines in industrial countries. This change took place during the late 1990s and in the early 2000s. Acellular vaccines contain purified antigens of B. pertussis including pertussis toxin (PT), outer membrane protein pertactin (PRN), filamentous hemagglutinin (FHA) and fimbriae 2 and 3 (Fim2/3) in different combinations and concentrations. However, many developing countries are still using whole cell vaccines for primary vaccination.

Despite extensive immunizations, pertussis is still one of the world’s worst controlled vaccine preventable disease. Epidemics occurred in many industrial countries, such as USA, UK, Australia and the Netherlands during last decade.

In Finland, pertussis vaccination was started in 1952 with whole cell vaccine, which was replaced by acellular vaccines in 2005. Last epidemic occurred in 2003-2004. During last 10 years, the number of reported cases varied from 200 to 500. There were also two infant deaths, one in 2014 and one in 2018.

What are the factors contributing to pertussis resurgence? Many studies have shown that the causes for the resurgence are multiple, such as increased awareness of disease, use of better laboratory diagnostic tools, improved surveillance methods and waning vaccine-induced immunity, especially from acellular vaccine-induced immunity and changes in B. pertussis bacterial population.

It is known that the laboratory methods used for diagnosis of pertussis are different in different laboratories and countries. To have comparable data, we need to harmonize and validate these methods. We started to work with ECDC (European Centre for Disease Prevention and Control) to write “Guidance and protocols for the use of real-time PCR and ELISA serology for laboratory diagnosis of pertussis”. PCR and ELISA are two main methods currently used for pertussis diagnosis in the world.

We then organized several external quality assurance (EQA) studies on PCR, serology and bacterial identification among the national pertussis reference laboratories of EU Member States. These EQA studies have resulted in greater harmonization in methods among different laboratories, showing a significant improvement of the PCR and ELISA methods used for diagnosis of pertussis in Europe.

We next conducted two large seroprevalence studies by which we could have a better picture of burden of this disease in Europe. The target age groups included adults aged between 20-39 and 40-59, who are the main source to transmit pertussis to their infants and children. With these studies we found that pertussis is more common than previously thought in Europe. These studies are the largest follow-up study in Europe since the Diphtheria-tetanus-pertussis vaccines were introduced. A very alarming finding in our research was the low levels of antibodies against diphtheria in many European countries. This clearly indicates that the herd immunity in middle-aged adults is decreasing. Attention should be paid to this matter in the entire Europe. The study has been recently published by Nature Communications. We are continuously working with ECDC for improved surveillance of pertussis.

To evaluate what changes have occurred in bacterial populations since acellular vaccines were introduced in Europe, we have compared B. pertussis strains collected during 1998-2015 from different countries with different time of introduction of acellular vaccines. We found a significant increase in circulating B. pertussis without expression of one vaccine antigen pertactin (PRN). The longer the period since the introduction of acellular vaccines, the higher the frequency of circulating PRN-deficient isolates.

We are continuously monitoring the effect of changes in bacterial populations on incidence and severity of this disease.

We are currently investigating immune responses in children and adults including how immunisations during pregnancy affect the immunity of their newborn babies. The studies are part of the EU PERISCOPE project with €28 million funding from the EU’s IMI2 and Horizon 2020 programmes.