Elena Mitsi, United Kingdom

Liverpool School of Tropical Medicine Clinical Sciences

Presenter of 2 Presentations

 Conference Calendar

PRECEDING PNEUMOCOCCAL COLONIZATION MODULATES NASAL AND LUNG MUCOSAL IMMUNE RESPONSES TO LIVE ATTENUATED INFLUENZA VACCINATION IN ADULTS (ID 323)

Session Name
Basic Sciences - Interaction with Microbiome, Viruses, other Bacteria
Presenter
Authors

HIGH LEVELS OF LUNG PNEUMOCOCCAL CAPSULAR-SPECIFIC IGG TO MOST VACCINE-TYPE SEROTYPES, BUT SEROTYPE 3, IN ADULTS VACCINATED WITH PCV13 (ID 577)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

Author Of 8 Presentations

 Conference Calendar

ASSESSING THE PROTECTION OF LIVE ATTENUATED PNEUMOCOCCAL VACCINES AGAINST EXPERIMENTAL HUMAN PNEUMOCOCCAL CARRIAGE (ID 1175)

Session Name
Vaccines - Pneumococcal Vaccines Development
Presenter
Authors

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.

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HIGH LEVELS OF LUNG PNEUMOCOCCAL CAPSULAR-SPECIFIC IGG TO MOST VACCINE-TYPE SEROTYPES, BUT SEROTYPE 3, IN ADULTS VACCINATED WITH PCV13 (ID 577)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

NASAL PNEUMOCOCCAL COLONIZATION ASSOCIATES WITH ALLERGIC INFLAMMATION IN CHILDREN (ID 779)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

USE OF PNEUMOCOCCAL TRANSCRIPTOMICS FROM MURINE AND HUMAN SAMPLES TO IDENTIFY NEW PROTEIN ANTIGEN VACCINE CANDIDATES (ID 1026)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

Abstract

Background

Conjugate vaccines successfully target specific serotypes but also lead to serotype replacement. Alternative strategies include bacterial proteins. Selection of protein antigens would benefit from knowledge of those most abundantly expressed during stages of human pneumococcal pathogenesis. Furthermore, vaccine protein candidates must also be expressed in mice for testing of candidates.

Methods

We designed a Nanostring codeset and analyzed 200 genes encoding for bacterial surface-exposed proteins. We evaluated transcriptomic expression in mouse colonization, pneumonia and sepsis models, as well as clinical CSF samples and human controlled infection.

Results

The 30 genes most highly expressed in each system (mouse model, human samples) were identified. There was excellent correlation between mouse colonization, pneumonia and blood specimens (R>0.85). Correlations between human colonization and meningitis were moderate (R=0.56), as were those between mouse and human transcriptomic profiles. We identified several genes highly expressed in all mouse and human conditions. Two in particular encoded for proteins that we show conferred protection against colonization and induced opsonic antibodies.

Conclusions

We present a novel approach to identify putative protective pneumococcal antigens, based on transcriptomic analyses of pneumococcal RNA harvested in different conditions. We identified two novel potential candidates, which also highlights the utility of studying pneumococcal gene expression from human samples.

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ASSESSING PNEUMOCOCCAL COLONIZATION NICHES (NOSE VS OROPHARYNX) IN YOUNG AND OLDER ADULTS DURING EXPERIMENTAL HUMAN PNEUMOCOCCAL CARRIAGE (ID 550)

Session Name
Basic Sciences - Conventional and Molecular Microbiology
Presenter
Authors

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.

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CHARACTERIZING THE IMMUNE RESPONSE TO EXPERIMENTAL PNEUMOCOCCAL CARRIAGE IN OLDER ADULTS (ID 682)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

THE MUCOSAL AND SYSTEMIC ANTIBODY REPERTOIRE FOLLOWING EXPERIMENTAL PNEUMOCOCCAL CHALLENGE IN HEALTHY ADULTS (ID 993)

Session Name
Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions
Presenter
Authors

Abstract

Background

In the experimental human pneumococcal challenge (EHPC) model, healthy adults are intranasally inoculated with a pneumococcal challenge strain. A panproteome Streptococcus pneumoniae array, containing over 2,600 pneumococcal proteins, was used to screen systemic and mucosal antibodies from EHPC volunteers.

Methods

IgG and IgA responses were profiled in a cohort of 150 volunteers challenged with serotype 6B pneumococci, half of whom were susceptible to experimental colonization and the other half remained protected. Serum and nasal wash samples collected pre- and post-EHPC were probed on the S. pneumoniae panproteome microarray with simultaneous detection of IgA and IgG binding.

Results

Hundreds of pneumococcal proteins were reactive with serum and nasal wash IgG and IgA. IgA- and IgG-reactive proteins showed high levels of overlap. However, over 200 proteins were reactive only with IgG. Antibodies against numerous proteins significantly increased following challenge. Unsupervised clustering showed subject-specific stability of antibody profiles in serum, but independently grouped profiles in nasal wash samples collected before and after challenge. No specific profile differences were observed in pre-EHPC samples between susceptible and protected groups, but the response to EHPC showed unique antigen reactivity patterns.

Conclusions

A single encounter with pneumococci can elicit broad changes in mucosal and systemic antibody responses to pneumococcal proteins.

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PRECEDING PNEUMOCOCCAL COLONIZATION MODULATES NASAL AND LUNG MUCOSAL IMMUNE RESPONSES TO LIVE ATTENUATED INFLUENZA VACCINATION IN ADULTS (ID 323)

Session Name
Basic Sciences - Interaction with Microbiome, Viruses, other Bacteria
Presenter
Authors