Fine Needle aSpiration of Lymph nodEs to Study vAccine-induced Immunity (SEA)

Optimisation of Lymph Node Fine Needle Aspiration to Study Pneumococcal Vaccine-induced Immunity

Rationale Causing a wide range of infectious diseases, including pneumonia, otitis media and meningitis, S. pneumoniae represents an important global health problem. Pneumococcal vaccines are clinically effective in preventing invasive pneumococcal disease, but the underlying immune response is likely to differ due to the inclusion of T cell epitopes in the conjugate, but not purified polysaccharide vaccine. However, these differences remain scantly studied. Lymph node fine needle aspiration (FNA) has been recently described to study vaccine-induced germinal centre responses in depth and represents a promising tool to study the underlying immune mechanisms of pneumococcal vaccines. Insight into the underlying immune mechanisms of vaccines could improve future vaccine design, e.g. by refining dosing intervals.

Objective Determine timing of peak germinal centre B cell frequency following pneumococcal vaccination.

Main trial endpoints The main trial endpoint is represented by the frequency of germinal centre B cells (BGC) in lymph node aspirates at various time points after vaccination, as measured by spectral flow cytometry. Both total BGC cells and S. pneumoniae polysaccharide-specific BGC frequencies will be determined.

Trial design Pilot intervention study without a comparator.

Trial population Healthy individuals between the age of 20 - 40

Interventions Subjects will be vaccinated once with Prevenar13. FNA of the draining lymph node will be performed and blood will be drawn at baseline, followed by weekly collection during the first four weeks, every other week between weeks 4 - 8 and a final collection time point after 12 weeks, resulting in a total of 8 sampling time points over the course of three months. Draining lymph node size will be assessed by ultrasound every other day during the first two weeks and then alongside lymph node FNA for the remainder of the study.

Study Overview

• Status: Recruiting
• Conditions: Vaccine-Preventable Diseases
• Intervention / Treatment: Drug: Pneumococcal Vaccine

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna H Roukens, MD, PhD; Phone Number: +31715262613; Email: a.h.e.roukens@lumc.nl
• Study Contact Backup: Name: Leo G Visser, MD, PhD; Phone Number: +31715262613; Email: l.g.visser@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333ZA
    • Recruiting
    • Leiden University Medical Center
    • Contact: Anna H Roukens, MD, PhD; Phone Number: +31715262613; Email: a.h.e.roukens@lumc.nl
    • Contact: Leo G Visser, MD, PhD; Phone Number: +31715262613; Email: l.g.visser@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants between the ages of 20 and 40 years old
• Participants should be generally healthy and without substantial co-morbidities, including all auto-immune diseases that are being actively treated with immunosuppressive therapy. Patients with chronic diseases that do not require immunosuppressive therapy and are stable, defined as not requiring change of therapy or hospitalization in the six weeks preceding study enrollment, might be eligible for this study.

Exclusion Criteria:

• BMI > 30 kg/m2
• Pregnancy at time of inclusion
• Breastfeeding during the course of the study
• Documented pneumococcal vaccination and/or infection
• Pneumococcal infection is defined as any infection that is microbiologically confirmed to be caused by S. pneumoniae (e.g. positive blood or sputum cultures for S. pneumoniae, positive urine S. pneumoniae antigen test)
• Documented HIV infection
• Documented primary immune disorder or primary coagulopathy
• Use of immunosuppressive medication or anticoagulants
• Known hypersensitivity to any of the vaccine components
• Recent (i.e. <4 weeks before inclusion) surgery in axillar area or major surgery elsewhere
• Vaccination with any vaccine < 1 month before inclusion
• Subjects vaccinated 1 - 6 months before enrolment can be included into the study. Study vaccine will be injected in the contralateral arm.
• Fever at time of inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pneumococcal vaccination arm; the participants will receive a registered pneumococcal vaccine according to manufacturers instructions	Drug: Pneumococcal Vaccine; vaccination with pneumococcal vaccine (PCV13); Other Names: vaccine with pneumococcal polysaccharides of 13 different serotypes conjugated to a protein (Prevnar13)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peak germinal center B cell count	frequency of germinal centre B cells (BGC) in lymph node aspirates will be measured at various time points after vaccination, as measured by spectral flow cytometry. Lymph node sampling will take place every week for the first 4 weeks, than every other week until week 8. Characterization of the lymphocytes in the lymph node aspirate will be performed by flow cytometry	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immune analysis of lymph node aspirates after pneumococcal vaccination	In addition to evaluating the frequency of (antigen-specific) BGC cells (outcome 1), we will perform phenotyping of these cells. Phenotyping includes measurement of activation markers, immunoglobulin class switching and markers associated with B cell differentiation.	3 months

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2023
• Primary Completion (Estimated): October 15, 2024
• Study Completion (Estimated): October 15, 2024

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: January 1, 2024
• First Posted (Estimated): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vaccine-Preventable Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: U1111-1285-0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: we will share data under restricted access, this is out institution's policy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No