Understanding how two common respiratory infections interact in the nose of healthy adults: Respiratory Syncytial Virus and Streptococcus pneumoniae

INTERVENTION: ‐The study has a follow‐up duration of 60 days and up to 9 clinical visits during that period. In Phase A: Up to 10 Healthy volunteers will be challenged with either Spn6B or RSV‐A at day 0 followed by a reciprocal challenge (RSV‐A or Spn6B) at day 7. Participants will be subject to confinement for 7‐10 days after either primary or secondary RSV‐A inoculation within a dedicated clinical research facility. This is to facilitate monitoring by a resident clinically trained member of the research team. During this phase we will assess safety of the co‐infection model and confirm the self‐isolation protocols. In Phase B/C: Up to 103 healthy volunteers will be challenged with either Spn6B or RSV‐A at day 0 followed by a reciprocal challenge (RSV‐A or Spn6B) at day 7. Participants will self‐isolate at home for 7‐10 days after either primary or secondary RSV‐A challenge, following self‐isolation protocols validated within Phase A. Phase A will also determine if it is feasible to proceed to Phase B without pre‐screening for pre‐existent levels of IgG to RSV. If fewer than 2 volunteers are infected with the challenge virus in Phase A, then Phase C will be conducted instead of Phase B. Phase C will be identical to Phase B, but the study population will be pre‐screened for RSV neutralizing antibody titres. In both phases longitudinal testing for pathogen detection will occur at 2, 7 and 14 days after challenge (final samples 60 days after primary challenge). Participants will be asked to visit our outpatient facility (wearing FFP2 masks and avoiding public transport) for sampling. The following samples will be collecting during the visits: nasal cells (small scrapes taken inside the nose); nasal wa CONDITION: Respiratory infections, respiratory syncytial virus and pneumococcus ; Infections and Infestations PRIMARY OUTCOME: Presence of Spn6B detected by classical microbiology in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60 INCLUSION CRITERIA: 1. Healthy adults aged 18��55 years (inclusive, at the time of consent) 2. Fluent spoken English – to ensure a comprehensive understanding of the research project 3. Capacity to provide written informed consent in English 4. Females of childbearing potential with a negative urine pregnancy test at screening and willing to practice adequate contraceptive measures as per UK Clinical Trial Facilitation Group during the study. 5. Willing to provide their household contacts with the Close Contact Screening Information Letter 6. For Phase C, RSV neutralising antibody titre in the lowest 10th percentile of screened participants SECONDARY OUTCOME: ; 1. Absence of SAEs measured in Phase A before progression to Phase B: Timepoints: Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 2. Presence of Spn6B detected by RT‐qPCR in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 3. Presence of Spn6B detected by combined RT‐qPCR and classical microbiology in at least one nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 4. Spn6B density detected by combined RT‐qPCR and classical microbiology in nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 5. Spn6B presence and density detected by combined RT‐qPCR and classical microbiology in nasal wash sample at any timepoint following Spn6B challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 6. Presence of RSV‐A detected by RT‐qPCR in at least one nasal wash sample at any timepoint following RSV‐A challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 7. RSV‐A presence and viral load detected by RT‐qPCR in nasal wash sample at any timepoint following RSV‐A challenge: e.g Day 2, Day 6, Day 9, Day 14, Day 21 and Day 60; 8. Number of URTI and LRTI symptoms per participant after secondary challenge. Timepoints: Day 9, Day 14, day 21 and Day 60; 9. Shedding of pathogens from the nose and throat will be assessed by:; 9.1.Coughing plate (Spn6B colonies detected by classical microbiology after Spn6B challenge: timepoints D2, D6, D9 and D14).; 9.2. Hand swab after nose touching (Spn6B colonies/DNA copies detected by classical microbiology and RT‐qPCR after Spn6B challenge: timepoints D2, D6, D9 and D14).; 9.3. Facemasks assessments (RSV viral load quantification by RT‐qPCR Spn6B colonies/DNA copies quantification by classical microbiology and RT‐qPCR; timepoints: D6 and D14); 10. Self‐collected home samples (nasopharyngeal swabs) collected once per week for 2 weeks from household contacts will be analysed for RSV‐A presence using RT‐qPCR.;