Presenter of 2 Presentations
O036 - IMMUNE RESPONSES TO A PNEUMOCOCCAL SEROTYPE-INDEPENDENT VACCINE CANDIDATE AND THEIR CORRELATION WITH PROTECTION AGAINST COLONISATION IN THE UK AND MALAWI. (ID 421)
Abstract
Background
Vaccines that confer serotype-independent protection and with low production costs are required to reduce the burden of diseases caused by Streptococcus pneumoniae (SPN). The development of these improved vaccines requires the identification of protein-based candidates that elicit protective immune responses. PnuBioVax (PBV) is a pneumococcal multi-protein vaccine candidate that has recently shown safety and immunogenicity in a Phase I Trial. We aim to investigate whether PBV-specific antibody levels and B cell numbers correlate with protection against Experimental Human Pneumococcal Challenge (EHPC) in cohorts form the UK and Malawi.
Methods
Pre- and post-inoculation sera and nasal wash samples from healthy volunteers previously enrolled in EHPC studies (Liverpool: SPN6B, 15B, 3; Malawi: SPN6B) were used to measure anti-PBV systemic and mucosal antibody titers. PBV-IgG-secreting memory B cells were assessed by ELISPOTs in pre- and post-inoculation PBMCs (SPN6B). Functionality of anti-PBV antibodies was determined by standardized agglutination assays using sera from PBV-immunized rabbits.
Results
Preliminary data showed that systemic anti-PBV antibody titres and PBV IgG-secreting memory B cells were increased post-inoculation in those volunteers colonised with SPN6B (Liverpool). In addition, in those volunteers colonised, high anti-PBV antibody titres pre-inoculation correlated with early clearance of colonisation. An increased number of PBV IgG-secreting memory B cells at baseline was observed in those volunteers protected against experimental colonisation.
Conclusions
These data suggest that anti-PBV responses could provide a correlate of serotype independent immunity. Further analysis will provide data for at risk populations and other SPN serotypes.
Acknowledgements: This project is funded by a BactiVac Pump-Priming award.
O090 - DEFINING THE RELATIONSHIP BETWEEN S. PNEUMONIAE COLONISATION DENSITY, BACTERIAL SHEDDING AND TRANSMISSION POTENTIAL (ID 699)
Abstract
Background
Colonisation of human nasopharynx with pneumococcus is the main reservoir of transmission and disease. Using a human exposure model, we previously demonstrated that hands can be vehicles of pneumococcal transmission, leading to acquisition of colonisation. Here, we used an experimental human pneumococcal challenge (EHPC) model to investigate pneumococcal shedding and the role of bacterial density and viral co-infection in shedding and transmission.
Methods
Healthy adults (aged 18-50 years) were inoculated with serotype 6B. Pneumococcal colonisation status and density were assessed in nasal wash samples collected pre- and at several time points after inoculation (D2, D6, D16, D22). Pneumococcal shedding was assessed in a) cough samples, b) facemasks and c) nose-to-hand swab samples at the same time points.
Results
Amongst the colonised subjects, 22.7% (17/75) shed pneumococcus at any time point, with 16% (12/75) of them expiring bacteria from the nose to their hand and 6.7% (5/75) from the mouth while coughing. Only 1 out of the 17 shedders expired bacteria from both nasal and oral route. Volunteers colonised with densities <102 CFU/ml of NW were identified as non-shedders, whereas shedding rates were linearly increased at density levels from 103 to 106 CFU/ml NW. Asymptomatic viral infection promoted pneumococcal shedding.
Conclusions
In this study, we described for the first time pneumococcal shedding in healthy colonised adults, who can also serve as a reservoir of transmission, and we demonstrated that density of colonisation is a major factor for bacterial shedding.