Ashleigh Howard, United Kingdom
Liverpool School of Tropical Medicine Clinical SciencesAuthor Of 2 Presentations
ASSESSING THE PROTECTION OF LIVE ATTENUATED PNEUMOCOCCAL VACCINES AGAINST EXPERIMENTAL HUMAN PNEUMOCOCCAL CARRIAGE (ID 1175)
- Helen Hill, United Kingdom
- Annie Blizard, United Kingdom
- M Gautan,
- Emily Gibbons,
- Ashleigh Howard, United Kingdom
- Angie Hyder-Wright,
- Simon P. Jochems, Netherlands
- Dessi Loukov, United Kingdom
- Daniella McLenaghan, United Kingdom
- Elena Mitsi, United Kingdom
- Elissavet Nikolaou, United Kingdom
- Sherin Pojar, United Kingdom
- Jesus Reine, United Kingdom
- Ryan Robinson,
- Elisa Ramos-Sevillano, United Kingdom
- Carla Solorzano, United Kingdom
- Stephen Gordon, Malawi
- Jeremy Brown, United Kingdom
- Daniela M. Ferreira, United Kingdom
Abstract
Background
We have previously reported that pneumococcal colonization increases lung and systemic protective immune responses. Live attenuated bacteria may be a good strategy for adult vaccination, particularly for those with chronic lung disease.
Methods
Single-blind RCT (superiority design). Healthy adults (age 18 to 50 years) were randomised 1:1:1:1 to be nasally vaccinated twice (two weeks interval) with either saline, wild-type 6B (BHN418) or a genetically modified strain (A1 or A2 – double mutants constructed on the BHN418 backbone). After 6 months, participants were challenged with wild-type 6B to assess protection against colonization acquisition.
Results
No Serious Adverse Events reported. 202 participants were assessed for eligibility, 148 randomised and 126 completed the study as per modified intention to treat. Rates of carriage acquisition following challenge with wild-type 6B were as follow: saline (negative control): 17/32 (47%), wild-type 6B (positive control): 9/31 (29%), A1: 9/30 (30%) and A2: 16/33 (49%).
Conclusions
Protection following nasal inoculation with attenuated strain (A1) was comparable to 6B wild-type. Attenuation in virulence by genetic modification may allow the development and safe use of live nasal vaccines whilst providing broad coverage against pneumococcal infection and improved lung immunity.
ASSESSING PNEUMOCOCCAL COLONIZATION NICHES (NOSE VS OROPHARYNX) IN YOUNG AND OLDER ADULTS DURING EXPERIMENTAL HUMAN PNEUMOCOCCAL CARRIAGE (ID 550)
- Elissavet Nikolaou, United Kingdom
- Esther L. German, United Kingdom
- Annie Blizard, United Kingdom
- Ashleigh Howard, United Kingdom
- Lisa Hitchins, United Kingdom
- Carla Solorzano, United Kingdom
- Sherin Pojar, United Kingdom
- Elena Mitsi, United Kingdom
- Syba Sunny, United Kingdom
- Felicity J. Dunne, United Kingdom
- Jenna Gritzfeld, United Kingdom
- Stephen Gordon, Malawi
- Daniela M. Ferreira, United Kingdom
Abstract
Background
Pneumococcal nasopharyngeal colonization is increasingly used as a surrogate marker for disease risk, thus accurate detection is crucial. However, it is not known if host age affects the colonization niche and, consequently, pneumococcal (Spn) detection in adults. Using the Experimental Human Pneumococcal Challenge (EHPC) model, we investigated if detection of pneumococcal carriage in the nose and oropharynx changes with increasing age.
Methods
Healthy adults (n=112) were intranasally inoculated with Spn6B and monitored for a month. Volunteers were split into young 18-55yrs (n=57) and older adults >55yrs (n=55). Colonization was determined by lytA and 6AB-specific multiplex qPCR assay in both raw and culture-enriched nasal wash (NW) and oropharyngeal swab (OPS). Colonization status was compared at 2, 7 and 14 days post-inoculation in both niches.
Results
We observed that the Spn6B colonization rate decreases with ageing in both NW (young 70.2%, older 50.9%) and OPS (young 64.9%, older 34.5%). Pneumococcal presence is higher in NW than OPS in both groups (young 70.2%-64.9% and older 50.9%-34.5%).
Conclusions
Pneumococcal presence in the nasopharynx is age-dependent. The nose, as assessed by NW sampling, seems to be the best niche for detection of pneumococcal colonization in adults, regardless of their age.