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.

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

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