Identification of correlates of protection against pneumococcal colonization

Professor Daniela Ferreira, Reader in Respiratory Infection Immunity and Vaccines
Liverpool School of Tropical Medicine (UK) Dr Joesph Campo 200x200px

Collaborators:
Dr Carla Solórzano-González, Liverpool School of Tropical Medicine (UK)
Prof Richard Malley, Boston Children’s Hospital (USA)
Dr Joseph Campo, Antigen Discovery Inc (USA)
Dr Eliane Miyaji, Instituto Butantan (Brazil)
Dr Imran Saleem, John Moores University Liverpool (UK)

SUMMARY
Pneumococcal disease is a public health threat that affects particularly vulnerable populations, such as children, the elderly, and those living in resource-limited conditions. Pneumococcus is an encapsulated bacterium and based on this capsule, it is classified in serotypes. There are >95 serotypes and licenced vaccines, based on capsular components, only protects against 13. These vaccines are expensive to produce, which limits the affordability and availability, especially in low and middle-income countries where the burden of the disease is the highest. Pneumococcus is found in the microflora that colonises the nasopharynx of healthy adults and children. This colonisation is the pre-requisite for disease and the reservoir for transmission. Novel vaccines must confer protection against colonisation. The correlates of protection against colonisation in humans are unknown and this information is needed to accelerate the development of improved vaccines. Protein-based vaccines could overcome the limitations of polysaccharide-based vaccines by protecting against all serotypes and reducing production costs. Together with the Boston Children’s Hospital (USA) and Instituto Butantan (Brazil), we generated the largest library of purified pneumococcal proteins and tested their capacity to elicit protective immune responses using samples derived from our Human Infection Model with Pneumococcus. Preliminary results have shown that a subset of these proteins elicit an immune response that correlates with protection against pneumococcal acquisition and control of density in those individuals colonised. We proposed a new partnership with Antigen Discovery, Instituto Butantan and Liverpool John Moores University to comprehensively identify correlates of protection against colonisation in a larger cohort and further develop the top protective antigens as vaccine candidates. Success will i) identify the cellular mechanisms that are involved in protection against pneumococcal colonisation, ii) identify novel protein-based vaccine candidates and iii) provide data to support funding applications to test the top candidates as nanoparticles formulation for a lung-delivered vaccine against pneumonia.