Summary
Whooping cough, known as pertussis, is a serious infection, especially in babies. Two types of pertussis vaccine exist: whole-cell (wP) and acellular (aP). aP vaccines may not be as effective in preventing whooping cough as wP vaccines, but the cause remains unknown. It may be due to differences in how these vaccines act at the surface (‘mucosa’) lining the inside of the nose and upper airway, where pertussis bacteria initially infect. Data from animal models show that immunisation with wP vaccines (but not aP) prevents pertussis bacteria infecting the nose, clearing them before any further symptoms develop and transmission to other individuals can occur. However, we do not know enough about the type of immune defence induced at the mucosa by the two different vaccines, and there is no data in children. Our project is set within a large study in The Gambia that is vaccinating babies with aP or wP vaccines. We will investigate components of the infant’s immune system activated by these vaccines at the mucosa, including cytokines and specific antibodies to pertussis bacteria. To achieve this, we will collect and analyse fluid from each infant’s nose. Blood samples are already being collected and we will add these valuable mucosal results to improve our insight into how these vaccines differ in their action. Our findings will help to design better pertussis vaccines in the future. This project links our opportunities and expertise in The Gambia to the UK and a wider European Consortium of academic and industry partners.
Project Outcomes
Although vaccines to prevent pertussis (whooping cough) have been given to infants for decades, whooping cough remains a serious respiratory illness, estimated to contribute to 160,700 deaths in children younger than five years worldwide. Two types of safe and effective vaccines are currently in use, but how long they might be protective for appears to vary between them: compared to an acellular type of vaccine, it looks as if the pertussis whole cell vaccine provides longer lasting protection and appears to also protect against colonisation with Bordetella pertussis in the nose, and not just disease in the lungs. However, it is known to have more side effects, and in many countries was substituted with the acellular type of pertussis vaccine several decades ago. Rises in cases of countries that had undertaken this switch have been observed, especially in young babies, and consequently, pregnant women are now also vaccinated to protect newborn babies from this potentially serious infection through passive transfer of antibody during later stages of pregnancy. This has been shown to be very successful in reducing cases in newborn babies. Nevertheless, to date, it is not established what an optimal pertussis vaccine should actually look like, as there is no validated so-called correlate of protection, and immunity appears to rely on both antibody and cellular immune responses.
We set out to understand the differences in immunity induced by either type of pertussis vaccine in African children, who were born to women who had either received pertussis vaccine in pregnancy or not. During this controlled clinical trial in The Gambia, we also wanted to understand the role of antibody and cytokines at the mucosal surface - in this case in the nose - that is induced by either type of vaccine and which might play an important role in preventing the organism causing whooping cough (Bordetella pertussis) to take hold. We therefore collected samples directly from the nose of the infants using a special filter paper to absorb secretions, which could be used to measure a variety of immune parameters.
This method had never been employed in African children in this context. We now have data that show the production of antibody and cytokines (immune mediators) in nasal secretions, and our ongoing work will relate these findings to the antibody and immune mediators induced in blood of the same infants. This will allow us to gain a more comprehensive understanding of what happens at the local and systemic level in response to the vaccination and what the impact might be on other bacteria that also live in the nose.
The BactiVac funding has facilitated to extend our research from looking at immunity in the blood stream to measuring immunity in the nose. Whilst our work is still ongoing, we expect that these findings will help us to further optimise pertussis vaccines going forward and hopefully understand in more detail what type of vaccine induces the strongest and most durable protection.