*Pertussis, also known as whooping cough, is a contagious disease caused by a type of bacteria called Bordetella pertussis. Symptoms can be more serious, and even deadly, in infants.*

Pertussis, also known as whooping cough, can be contracted by people of all ages. The disease is mostly mild in adults – but whooping cough poses more of a threat to infants under one-year-old and can even be fatal. Could a human challenge trial help researchers pinpoint a way to improve pertussis vaccines and give us better immunity?

Whooping cough is one of the leading causes of death among unvaccinated children, mainly in developing countries and areas where vaccine rates are low. Each year, 20–40 million cases of pertussis are reported around the world, and approximately 400,000 of those cases are fatal (Source).

Vaccines for pertussis have been in use for decades. These immunizations have greatly reduced the spread of the disease and protected many people from severe illness and death. The Government of Canada reports that from 1935 until 1945 (two years after the first pertussis vaccine was introduced in Canada), there were over 15,000 annual cases of pertussis in Canada. As immunization became more widespread, cases declined. By 1965, 20 years after the vaccine was first introduced, there were less than 5000 cases per year. However, pertussis is still endemic (regularly found) today. It is easily transmitted and infants who are too young to be protected by a full vaccine series are especially vulnerable.

“As immunization became more widespread, cases declined. By 1965, 20 years after the vaccine was first introduced, there were less than 5000 cases (of pertussis) per year.”

About pertussis (whooping cough)

Pertussis, also known as whooping cough, is a contagious disease caused by a type of bacteria called Bordetella pertussis. In adults the disease is relatively mild. Symptoms include mild fever, runny nose, red watery eyes, and a cough. Serious coughing fits can last 2 to 8 weeks and can cause choking, vomiting, and difficulty breathing. Symptoms can be more serious in infants due to their narrow airway passages. Pertussis-induced coughing fits end with a gasp for air that produces the whooping sound that the disease is named for.

Cases of whooping cough are on the rise

Cases of pertussis began increasing again in Canada in the late 1980s. Though case numbers and death rates are still lower than they were before vaccines, the increasing cases put infants and other vulnerable people at higher risk of exposure.

There are a few reasons this increase could be happening:

Protection by current vaccines is less than ideal
New strains of pertussis may be stronger or better at infecting us
We are keeping track of cases more than before
The cyclical and sporadic nature of pertussis - cases rise and fall in cycles/waves, and the cycles don’t follow a predictable pattern (Source, Source)

All these factors could be contributing to the rise in case numbers. But the main culprit behind pertussis increasing again seems to be a decrease in our immunity to the disease. (Source)

A need for better immunity

Immunity to whooping cough can disappear in as little as two years, depending on what kind of vaccine a person had. (Source)

When immunity has faded, the immune system will take longer and/or fail to respond to a threat from that disease. This could give the infection more of a chance to make us sick.

Rapidly decreasing immunity like this can make it more difficult to develop herd immunity, where the presence of a mostly-vaccinated community cocoons vulnerable individuals (such as the immunocompromised or those who cannot be or who are not yet vaccinated) from severe illness. This is especially important with pertussis, because many vulnerable people like infants get the disease from adults or older children in their lives. When people lose most of the immunity from childhood vaccinations, they are even more likely to get sick and pass pertussis on.

When the people around an infant are mostly vaccinated, the community immunity helps protect the more vulnerable child. This is harder to achieve with pertussis, as immunity wanes very quickly - sometimes within two years.

It’s unclear why the type of vaccines we use in Canada (acellular vaccines) and natural infection don’t produce more effective, longer-lasting immunity. There have been multiple research studies conducted on pertussis, but we don’t yet know enough to determine why acellular vaccines aren’t providing longer-lasting immunity. Unlocking those answers would help us create new vaccines that give us better protection against the disease.

A human challenge trial help us find answers

In a human challenge trial, healthy, informed, consenting participants are intentionally and safely exposed to a disease, closely monitored, and their immune responses are studied. The Canadian Center for Vaccinology (CCfV) is conducting a human challenge trial to learn more about pertussis and build a foundation for future research with the ultimate goal of developing more effective vaccines. The study is the first of its kind for pertussis in North America.

Why conduct a human challenge trial instead of another type of study?

The questions we have about pertussis can’t be fully answered with animal studies alone, as pertussis only naturally infects humans. A human challenge study may be the edge researchers need to figure out why long-term immunity to whooping cough is not acquired after vaccination or natural infection.

A human challenge trial lets us observe how the human immune system responds to pertussis in the earliest stages of exposure. Researchers can collect daily samples to better understand how the bacteria that causes the disease is acting in the body. Read more about the advantages of human challenge trials

Previous challenge studies on pertussis

A human challenge trial on pertussis has been conducted in recent years by the PERISCOPE consortium in the UK.

This study added to the global understanding of pertussis and our understanding of the infection before symptoms. It also provided an important framework for a pertussis challenge trial, proving that these trials can be done safely and effectively with Bordetella pertussis with the dose of bacteria they exposed participants to. Pertussis is a good candidate for challenge studies in adults not only because the disease is mostly mild in that age group, but also because there is a readily available, highly effective treatment that can halt the infection.

How CCfV’s trial will add to global knowledge

CCfV is conducting two consecutive human challenge trials to build on the PERISCOPE study, observing a slightly later stage of the disease’s progression. These trials will add to and strengthen the knowledge we gained from the PERISCOPE study and show us if the results are similar in additional studies among different populations.

CCfV’s trial is modelled after a North American variant of Bordetella pertussis, while the PERISCOPE trial studied a variant common in Europe. This will provide data more relevant to the North American environment.

The trials CCfV are conducting have two main goals:

To help confirm the best dose (amount of bacteria) to expose participants to. Researchers need to determine what dose is required for the immune system to react and the participant to only experience mild symptoms.
To allow researchers to learn more about how pertussis progresses in the human body from exposure to mild disease.

How will the challenge study work?

Healthy, informed, consenting participants will be intentionally exposed to pertussis in a controlled environment, then monitored by healthcare staff during an inpatient stay in CCfV’s fully-equipped challenge unit. There will be daily scheduled tests (such as EKGs, blood pressure readings, nasal washes and blood tests).

The dose of bacteria has been carefully planned to produce mild symptoms, and this strain of bacteria was chosen for how effective antibiotics are in treating it. Participants will be given antibiotics to completely clear the infection at a pre-planned point so that the illness won’t become more serious.

After the inpatient part of the study, researchers will follow up with participants for a year.

Healthy, informed, consenting participants will be intentionally exposed to pertussis in a controlled environment, then monitored by healthcare staff during an inpatient stay in CCfV’s fully-equipped challenge unit.

Global impacts

Human challenge trials around the world have made a meaningful difference. They have aided in vaccine development, improvements to medical treatments, and more. What CCfV learns from this Human Challenge Trial will help build a stronger foundation for future studies on pertussis, pushing us one step closer to improved vaccines and better protection against this disease.

You can help make a difference in your own community and beyond by volunteering for the study. The pertussis human challenge trial is recruiting healthy participants ages 18-40. Learn more about what it’s like to take part in a trial by visiting our participant page:

Learn more

The problem with pertussis, and how a human challenge trial could help