A ground-breaking new trial offers explanations for differences in pneumococcal vaccine effectiveness between populations in the Global North and Global South and paves the way to inform improved strategies to prevent severe pneumonia.
Pneumococcal bacteria are commonly found in the human nose (we call this carriage) and do not cause disease for the majority of people, but this is the mechanism by which infections spread (“coughs and sneezes spread diseases”). In addition, in vulnerable individuals the pneumococcus can invade past the nose and cause severe disease including pneumonia, sepsis and meningitis, and is a major cause of death throughout the world. An effective pneumococcal vaccine should prevent the bacteria from growing in the nose, prevent spread of infections and reduce the risk of severe disease. Pneumococcal conjugate vaccines (PCV) have dramatically reduced pneumococcal disease around the world by preventing or reducing carriage. The reduction in spread of infection has led to a ‘herd effect’ among unvaccinated populations. In Malawi, the PCV13 vaccine has resulted in substantial reductions in pneumococcal disease in vaccinated children by preventing severe disease but there are still high rates of pneumococcal carriage among vaccinated children. This increases the risk of transmission to unvaccinated children and vulnerable groups such as people living with HIV, reducing the ‘herd effect’ in these populations.
About the study
This study was designed to find out if PCV13 was protective against experimental human pneumococcal carriage in Malawian adults. The trial design builds on extensive experience with the controlled human infection model (CHIM) in Liverpool and Blantyre, Malawi. More than 2000 participants have received pneumococcus in this way, none developing serious side effects. In this study, 278 healthy Malawian adults were recruited to a double-blind randomised control trial. Half of the study volunteers were given a vaccine against pneumococcal disease (PVC13 injection) and the rest a placebo (saltwater injection). Four weeks later (the time taken for the immune system to respond to the vaccine), all the volunteers were given a small dose of pneumococcal bacteria via their noses. Researchers found that across the trial those who had received the vaccine had lower rates of pneumococcal bacteria colonising their noses than those who had received the placebo; vaccine efficacy was rated as 62%. This was less than a similar study conducted in the UK where vaccine efficacy was 78%.
Why is this important?
This study is important for several reasons. First, it was the first vaccine trial using a bacterial human infection study or CHIM in Africa and provides important data demonstrating the safety of this approach to understand vaccine effects in populations that need them most. Secondly, the researchers found that the vaccine was less effective in Malawian compared to UK participants using a similar study design. They will now use participant samples taken during this study to understand if and how the immune system responds differently to the vaccine between populations. The partnership between LSTM (studies UK populations) and Malawi Liverpool Wellcome Research Programme (MLW) is unique in that it will allow the researchers to directly compare effects between populations to understand how vaccines can be improved to prevent severe disease and save lives.
Stephen Gordon from MLW, who led the study, said:
“This landmark study, the first human challenge study in Malawi and the first study of its kind in Africa, paves the way for pneumococcal vaccine research and further human infection discovery. We can now explore better pneumococcal vaccination strategies to protect vulnerable people, such as people living with HIV, and to protect against strains for which no current vaccine is effective. We can also explore the potential of human challenge studies in diagnosis and prevention of other infections, such as salmonella and tuberculosis.”
In trying to understand these results, it should be noted that a similar study using UK-based individuals showed higher levels of protection than that in Malawi, but there was higher natural exposure to pneumococcal bacteria in the community among the Malawi participants. This requires further evaluation using longitudinal immunological samples and the pooling of Malawi and UK data.
Ben Morton from LSTM, who developed and implemented the study in Malawi, said:
“It is fantastic to see the culmination of many years of work demonstrating safety in the UK; exploring acceptability; and completing feasibility studies to make sure it was safe and possible to do this work in Malawi. This trial provides essential data to underpin epidemiological observations of reduced herd immunity effects from pneumococcal conjugate vaccine in sub-Saharan Africa populations compared to populations in the Global North. As our work progresses and we explore how vaccine immune responses differ in samples taken from trial participants we are in a unique position to inform improved vaccination strategies to protect populations vulnerable to pneumococcal disease.”
Human infection trials – the podcast
Human infection trials, such as the one used in this study, are a quick and effective way to gather data. Wellcome, which funded this research, recently produced a podcast on the model featuring Dr Dingase Dula of Malawi Liverpool Wellcome Research Programme. In the podcast, Dr Dula talks about this trial and the benefits of the model in general. Listen here.