Daniela M. Ferreira, United Kingdom

Liverpool School of Tropical Medicine Clinical Sciences

Poster Author Of 1 e-Poster

Online Abstracts Vaccines - Pneumococcal Vaccines Development C1 Pneumococcal Vaccines Development

Presenter of 1 Presentation

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

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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Author Of 9 Presentations

THE IMMUNOGENIC EFFECTS OF CHITOSAN COATINGS ON PLGA NANOPARTICLES FOR VACCINE FORMULATIONS (ID 712)

Abstract

Background

One approach of novel mucosal vaccines is the use of chitosan, which has shown potential as a versatile and effective coating material on nanoparticles (NPs) for improving efficacy. Various mechanisms are recognised to lead to improved immune response, however it is unclear how variations of chitosan molecules with differing properties affects the immunogenicity on dendritic cells (DCs). This study investigated the effects of different chitosan on the coating properties on PLGA NPs and subsequent immunogenicity.

Methods

Chitosans with varying molecular properties were coated onto PLGA NPs. The resulting NPs were characterised for size and zeta potential, quantification of chitosan adsorption on the NP surface, and immunogenicity through expression of CD40, CD86.

Results

PLGA NPs with different chitosan coatings exhibited differing particle characteristics, degrees of adsorption, and subsequent surface adsorption of model antigen protein. The relationship between the amount of chitosan adsorbed onto the particle surface and the resulting NP size increase differed for each chitosan. As expected, the surface charge also varied greatly, and the chitosans exhibited a concentration dependent immunogenicity.

Conclusions

Coating PLGA NPs with differing forms of chitosan, including salt form, degree of quaternisation, molecular weight, oligomerisation, carboxymethylation, all contribute to NPs containing unique characteristics and immunogenicity.

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

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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MUTATIONS OF STREPTOCOCCUS PNEUMONIAE BIOSYNTHESIS GENES INFLUENCE EPITHELIAL MICRO-INVASION AND THE INNATE-EPITHELIAL CELL RESPONSE IN VITRO AND IN AN EXPERIMENTAL HUMAN PNEUMOCOCCAL CHALLENGE MODEL (ID 872)

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

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

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

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.

Hide