Summary
Streptococcus pyogenes, also known as Strep A, is a bacterium that causes severe infections in humans. Approximately half a million people die from Strep A infections each year, predominantly in low resource settings. The creation of a vaccine to protect against Strep A is therefore a top priority. However, progress is slow in part due to our limited knowledge of exactly how the immune system responds to Strep A and provides protection against infection. One of the challenges in creating a vaccine is knowing which parts of the bacteria to target. There are two main strategies in the development of a vaccine; 1) targeting parts of the bacteria that would be present in all strains and 2) targeting the parts of the bacteria (the M protein) which make each strain unique.
Our aim is to understand how antibodies develop with increasing age and following exposure to unique strains of bacteria, and to explore the extents that antibodies generated to unique strains protect from infection.
In our research, we will use samples collected over one year from 442 people in The Gambia where rates of infection were high. We will measure antibodies by expanding a technique we have already developed at the MRC Unit The Gambia. We will explore if antibodies to particular strains are associated with reduced risk of infection from that strain, from similar strains and from unrelated strains. This understanding will help guide the strategy to eventually role out the most effective vaccine against Strep A in high burden settings like The Gambia.
Project Outcomes
This project aimed to better understand how the body’s immune system protects against Streptococcus pyogenes (Strep A), a bacterial infection responsible for many deaths worldwide. Our focus was on studying specific immune responses to different types of Strep A proteins, known as M proteins, which vary greatly across different strains of the bacteria. These proteins might be important targets for vaccines, but we need to know more about how our immune system responds to them to develop effective vaccines.
To investigate this, we developed and optimized a specialized test called a multiplex assay, which can measure immune responses (IgG antibody levels) to many different M proteins at once. We selected 22 M proteins for the test, ensuring they represented the most common and important types found in our study population in The Gambia. We also included some proteins that are part of current vaccine candidates.
Our test successfully measured antibody levels in samples from participants in a Gambian study on Strep A infections. We found that antibody levels generally increased with age, suggesting that repeated exposure to different Strep A strains helps build immunity over time. We also observed that participants who had higher antibody levels to multiple M proteins were less likely to have a confirmed Strep A infection in the future.
However, we faced challenges with the specificity of our test—meaning that in some cases, the test could not clearly distinguish between antibodies targeting different M proteins. Despite these challenges, our findings support the idea that natural immunity to Strep A develops as people are repeatedly exposed to various strains of the bacterium. This insight is valuable for designing vaccines that could mimic this natural immunity and protect against a wide range of Strep A strains.
Our ongoing work aims to refine our understanding of these immune responses and contribute to the development of safe, effective, and widely accessible Strep A vaccines, particularly for regions like The Gambia, where the disease burden is high.
Dr Alex Keeley
Wellcome Clinical PhD Fellow in Global Health
MRC Unit The Gambia at London School of Hygiene and Tropical Medicine
The Gambia/UK
Collaborators:
Dr Claire Turner, Royal Society/Wellcome Trust Sir Henry Dale Research Fellow, University of Sheffield, UK
Professor Thushan de Silva, Professor of Infectious Diseases, University of Sheffield, UK
Fatoumata Camara, Scientific officer, MRC Unit The Gambia at LSHTM, The Gambia/UK
Dr Gabrielle de Crombrugghe, F.R.S - FNRS Clinical PhD Fellow, Université Libre de Bruxelles (ULB), Belgium
Professor Pierre Smeesters, Professor of Paediatric Infectious Diseases, Université Libre de Bruxelles (ULB), Belgium
Professor Anne Botteaux, Associate Professor, Université Libre de Bruxelles (ULB), Belgium