Whooping cough exposure improves response to booster vaccine Taking exposure into account gives more insight into vaccine efficacy

Older children have more antibodies against the whooping cough bacteria than younger children, because they have been exposed to the pathogen more often. They also show a stronger immune response after a booster vaccination against whooping cough. Thus, exposure is an important factor in the timing and efficacy of vaccines. This is shown by the Radboud university medical center in Nature Communications.

The Netherlands has been vaccinating its population against whooping cough (also called pertussis) since 1957. It is the "P" in the DTP-IPV vaccine, which children receive three times in their first year of life, and again when they are four years old. However, the bacterium that causes whooping cough still circulates and causes disease. That's because whooping cough vaccines protect very well against serious illness, but not as well against infection with the highly contagious whooping cough bacterium.

What is the effect of circulating whooping cough bacteria on a booster vaccination? That’s the question that immunologist Dimitri Diavatopoulos and PhD student Janeri Fröberg of the Radboudumc tried to answer. They studied two groups of children. 'One group was between 7-10 years old, the other between 11-15 years,' Fröberg says. 'They had all received their series of shots from the National Vaccination Program. We gave them a booster vaccine and investigated the immune response in the nose, before the booster, and one month and one year afterwards. In our analysis, we distinguished between antibodies against the vaccine and against the bacteria themselves.’

Disease notifications

What they first noticed: before giving the booster vaccination, the older group of children already had more antibodies against the whooping cough bacteria than the younger group. 'This was likely due to exposure to the bacteria,' says Diavatopoulos. 'Older children have simply had more exposure to the bacteria since their last vaccination. But whooping cough outbreaks are often very localized, so exposure can vary greatly by region and age group.' To check the exposure, the researchers delved into the regional data on whooping cough disease notifications, made available by RIVM. 'We indeed saw more disease notifications due to whooping cough in the older group.'

Following up from this, the researchers studied the immune response to the booster vaccination. Fröberg: 'In the group with older children, we saw more antibodies to the vaccine in the nose after vaccination, and a slower decrease in antibodies from a month to a year after the booster. We thought this was a very interesting finding. It could mean that exposure to the pathogen leads to more durable antibodies in the nose after a booster vaccination, and thus possibly protection against the disease. Conversely, a booster vaccination without exposure may give a shorter-lived immune response.’

Understanding

The degree of exposure to a pathogen appears to be important for the response to a vaccine, with potential implications for the vaccination program. 'Different countries vaccinate against whooping cough at different ages, and the number of booster vaccinations also varies,' Diavatopoulos explains. 'In the Netherlands, we give children a booster at the age of four, while in other countries this is done, for example, at the age of nine or twelve. In the Dutch vaccination program, the timing of the booster will soon shift as well, from four to six years old. Our study supports this later administration of a booster. However, we do have to keep in mind the right balance between the circulation of the bacteria and the severity of symptoms in people who become infected. Some exposure might be favorable for the vaccine response, but the burden of disease must remain sufficiently low.'

That vaccines provide good protection against disease, but less against spread, is something we have heard more often in recent years. 'We see parallels with the corona pandemic,' Diavatopoulos explains. 'There, too, the immune response is an interplay between vaccination and exposure. The sum of those factors influences how well a vaccine works and to what extent you are protected. As far as I'm concerned, we should take exposure into account in every study of a new vaccine; this will give us much more insight into protection.'

About the publication

This publication is part of the IMI2 project PERISCOPE No. 115910, which received funding from the European Commission. The study was published in Nature Communications: Prior exposure to B. pertussis shapes the mucosal antibody response to acellular pertussis booster vaccination. Evi van Schuppen, Janeri Fröberg, Prashanna Balaji Venkatasubramanian, Pauline Versteegen, Hans de Graaf, Jana Holubová, Joshua Gillard, Pieter G. M. van Gageldonk, Irma Joosten, Ronald de Groot, Peter Šebo, Guy A. M. Berbers, Robert C. Read, Martijn A. Huynen, Marien I. de Jonge & Dimitri A. Diavatopoulos. DOI: 10.1038/s41467-022-35165-w.

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