The impact of vaccine platform, age and HIV infection on germinal centre formation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

6 Mar 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

NWO Vidi · ZonMw clinical fellowship

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The primary objective of the trial will be to compare germinal centre formation after pneumococcal vaccination between different populations (health young vs healthy older adults; healthy young vs people living with HIV) as well as between different vaccine platforms.

Secondary objectives 9

1. Comparison of long-term immunological memory formation between populations and vaccine platforms.
2. Identification of a basline immunological signature predictive of germinal centre and/ or long term immunological memory formation.
3. Identification of peripheral blood correlates of germinal centre reactivity and memory formation
4. Impact of age and/ or HIV infection status on formation of long-lived immunological memory.
5. Identifying clinical risk factors associated with germinal centre formation.
6. Identifying clinical risk factors associated with long-term immunological memory formation.
7. Evaluating the effect of pneumococcal colonization at the time of vaccination with serotype specific immune responses post vaccination.
8. Difference in lymph node reactivity between age group and PLWH.
9. Difference in lymph node reactivity between vaccine platforms.

Conditions and MedDRA coding

HIV infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age between 20 - 40 years or age > 60 years.
2. Generally Healthy
3. For PLWH group: aged 20 - 40 years, with documented HIV infection on active anti-retroviral therapy resulting in viral supression ( HIV copies < 200/ml)

Exclusion criteria 15

1. Pregnancy at time of inclusion
2. Vaccination < 1 month before inclusion
3. Fever at time of inclusion
4. Inability to provide informed consent
5. Inability to visit the LUMC for study procedures.
6. Breastfeeding during the course of the study
7. Prior documented pneumococcal vaccination
8. Prior pneumococcal infection
9. Documented primary immune disorder or primary coagulopathy
10. Use of immunosuppressive medication
11. Use of direct acting anticoagulant drugs (DOACs) or vitamin K antagonists
12. Known hypersensitivity to vaccine components
13. Recent (past month) surgery in axillar area or major surgery elsewhere
14. Chronic nasal corticosteroid use (> 3 months)
15. History of severe nose bleeds

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Immunophenotyping of lymph node FNA samples (% germinal centre B cells and %T follicular helper cells), 4 weeks after vaccination.

Secondary endpoints 9

1. Immunophenotyping of PBMC's 6 months after vaccination (% S. pneumoniae PS-specific B cells per serotype, Spn PS-specific B cell phenotype, Spn PS-specific antibody titres, Spn PS-specific antibody fuctionality, CRM-197 specific B cells and T cells.
2. Serum and lymph node supernatant biomarkers at day 7, day 28 and day 72 post vaccination
3. Immunophenotyping and functional analysis of PBMCs at baseline
4. Serum biomarkers at baseline.
5. Pneumococcal serotype specific colonisation in saliva
6. lymph node size in cortical thickness, long axis and short axis (determined by ultrasound)
7. Comparing Spn PS-specific antibody titres in saliva to Spn PS-specific antibody titres in peripheral blood.
8. Association between diet, excercise, alcohol consumption, smoking, comorbidities, medication, clinical Frailty score, CD4+ T cell count and immune response (% Bgc cells and Tfh cells, 4 weeks after vaccination).
9. Pneumococcal serotype specific colonisation in saliva and its association with post vaccination serotype specific B cells, serotype specific antibody response and OPA-titres in peripheral blood.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

dr A.H.E. Roukens

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

dr A.H.E. Roukens

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications