Training tomorrow’s vaccine developers
The EU-funded VACTRAIN project comprised a network of academic and industrial partners. The goal was to train 11 early stage researchers in vaccine development. Scientific work involved the investigation of the molecular, immunological and biochemical properties of several infectious agents using state-of-the-art technologies. Trainees employed next generation sequencing techniques to perform transcriptome profiling of Mycobacterium tuberculosis-infected lungs and identify genes that predict the clinical outcome in cytomegalovirus (CMV)-infected new-born babies. In addition, researchers worked towards the discovery of antigens that are capable of stimulating protective immune responses in humans. Long term the aim was to improve the kinetics and characteristics of protective immune responses against different pathogens. The consortium focused on antigens expressed early or expressed during infection by many subspecies. The immunogenicity of the selected antigens was tested in vivo with promising results, demonstrating potential clinical relevance. With respect to tuberculosis and CMV, antigens that activated T cell responses early during infection were also identified. Considerable effort went towards understanding the mechanism of immune-mediated CMV control induced by CMV-specific antibodies as well as protective CD4 and CD8 T cells using synthetic long peptides. A phase II trial of a CMV glycoprotein B vaccine was also performed. Results demonstrated that the vaccine boosted neutralising antibodies only in patients previously exposed to CMV. Protection was only associated with a particular antigenic epitope, indicating that future efforts should concentrate on components of the immune system that are protective against CMV infection. In another part of the study, researchers identified a genetic component that regulates Staphylococcus aureus pathogenicity. Additionally, they found that a broadly protective flu vaccine provided protection in a mouse model of Influenza-Staphylococcus aureus co-infection, underscoring the importance of influenza immunisation as an anti-pandemic strategy. Taken together, the activities of the VACTRAIN project will help develop effective vaccines against tuberculosis and also reduce the long-term neurodevelopmental consequences of congenital CMV infections. Considering the high prevalence of these pathogens and the anti-microbial resistance seen in Staphylococcus aureus, these findings will provide novel treatment solutions.
Keywords
Vaccine, VACTRAIN, Mycobacterium tuberculosis, CMV, Staphylococcus aureus
