Application of antibody immunoprofiling to study the immune responses to acellular pertussis vaccine in pregnancy

Summary 

Despite the availability of vaccines, whooping cough (pertussis) remains a leading cause of vaccine-preventable deaths, particularly in children under five and Sub-Saharan Africa. One reason for this is the switch that occurred from the whole-cell (wP) to the subunit acellular (aP) pertussis vaccine within childhood immunisation schedules. It is widely accepted that aP vaccination, while protecting against severe disease, has a shorter duration of protection and requires frequent booster doses. Importantly, boosters are recommended in pregnant women to reduce deaths in newborn infants. Our previous work conducting vaccine trials in The Gambia suggests that levels of antibody to vaccine antigens may be significantly reduced in infants born to mothers who received the pertussis vaccine in pregnancy. In this study we will use a method, termed microarray antigen profiling, to compare the antibody responses in mothers and infants. This method produces a ‘fingerprint’ response for each vaccine recipient, providing information on the targets for the antibodies produced. We can use machine learning methods (a type of AI) to map antibody responses to various parts of the pertussis toxin which is used in the aP vaccine. This is a small scale, proof of principle study which could lead to more detailed investigations into the longer-term immunological impact of pertussis immunisation during pregnancy. It may help to design more effective maternal and infant vaccine strategies, particularly in poorer countries where pertussis vaccines are often not routinely given in pregnancy.

Project Outcomes

Whooping cough is caused by the bacterium Bordetella pertussis and is one of the leading causes of vaccine-preventable deaths worldwide. The infection particularly affects children under five and populations from Sub-Saharan Africa; it is a leading cause of vaccine-preventable deaths. One reason for this is the switch that occurred from the whole-cell (wP) to the subunit acellular (aP) pertussis vaccine within childhood immunisation schedules. It is widely accepted that aP vaccination, while protecting against severe disease, has a shorter duration of protection and requires frequent booster doses. Importantly, boosters are recommended in pregnant women to reduce deaths in newborn infants. Our previous work conducting vaccine trials in The Gambia suggests that levels of antibody to vaccine antigens may be significantly reduced in infants born to mothers who received the pertussis vaccine in pregnancy. In this study we have used a method, termed microarray antigen profiling, to compare the antibody responses in mothers and infants. The aP and wP vaccines are complex, consisting of multiple protein components. Following vaccination, antibodies are produced against these components- in the case of this project, our focus is on protein antigens. To analyse the antibody responses, we prepared a dedicated microarray, which contains fragments of protein antigens, in the form of peptides, which are immobilised onto a glass slide. Antibodies from the serum of vaccinated individuals are then bound to the peptides. In this way, the antibody responses to these individual components form a ‘fingerprint’-type response for each vaccine recipient. We can then compare these fingerprint profiles against each other:  machine learning methods (a type of AI) are particularly powerful at picking out these patterns. Using this approach, we were able to show that there was clear differentiation between antibodies from mothers and infants up to 9 months after birth. Shortly after birth, at the 2-month timepoint, profiles from the infants suggest that they originate from transmission of maternal antibodies. 9 months after delivery, however, the pattern associated with maternal antibody faded and the remaining profiles were attributable to antibody responses from the infants. This study represents proof of principle that peptide microarrays can play a useful role in understanding how vaccination of mothers may help transmit immunity to their children. This could lead to more detailed investigations into the longer-term immunological impact of pertussis immunisation during pregnancy. It may also help to design more effective maternal and infant vaccine strategies, particularly in poorer countries where pertussis vaccines are often not routinely given in pregnancy.