Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2)

Introduction
Despite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).

Methods and analysis
Healthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.

Ethics and dissemination
The study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.

Trial registration number
ISRCTN15728847, NCT04974294.

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Luglio 2022

Abstract 13: 3D-Map Analysis Of Symptomatic Intracranial Atherosclerotic Plaques

Stroke, Volume 53, Issue Suppl_1, Page A13-A13, February 1, 2022. Background:The study of plaque enhancement using high resolution vessel wall imaging can provide useful prognostic data. However, this analysis is hindered by plaque sampling and methodological constrains. We developed a new method to quantify plaque enhancement with 3D map analysis.Methods:Ultra-high resolution (7 Tesla) vessel wall imaging was performed on 41 patients with history of symptomatic atherosclerotic disease. Culprit and non-culprit plaques were analyzed. 3D reconstructions of culprit (N=41) and non-culprit plaques (N=14) was performed on T1 and T1+Gd images. Using an in-house code, orthogonal probes were extended from the lumen of the vessel into the arterial wall (Figure). In this way, the entire wall was sampled with multiple spokes. These values were then normalized to the corpus callosum (CC) to obtain a signal intensity ratio (SIratio). Dynamic contrast uptake was quantified as the change in mean SI of the plaque after contrast administration.Results:Forty one culprit and 14 non-culprit plaques (N=55) were analyzed. Culprit plaques enhanced with gadolinium (Gd) more significantly (SIplaque= 0.76 ± 0.28) than non-culprit plaques (SIplaque=0.58 ± 0.14) (p=0.05). In addition, culprit plaques displayed more contrast uptake (ΔSIplaque=0.33±0.25) than non-culprit plaques (ΔSIplaque=0.19 ± 0.08,p=0.01).Conclusion:3D analysis of plaque enhancement with ultra-high resolution MRI is a promising technique that may be used as a biomarker of culprit intracranial atherosclerotic plaques. In addition, quantifying the dynamic plaque contrast uptake may provide more insight into the biology of these lesions.Figure. Magnified 7T coronal view of a basilar artery plaque pre (A) and post administration of Gd (B). 3D analysis of the dynamic uptake of Gd in T1 (C) and T1 + Gd (D). This plaque had a of 0.49 = highly enhancing.

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Febbraio 2022