Identifocation the B Cell Subsets Responsible for Anti-pneumococcal Response (PNEUMOVACB)

August 22, 2025 updated by: Institut National de la Santé Et de la Recherche Médicale, France

Analysis of the Response of Healthy Adults to a 23-valent Pneumococcal Polysaccharide Vaccine to Identify the B Cell Subsets Responsible for the Production of IgM, IgG2 and IgA Anti-pneumococcal Capsular Polysaccharides

The purpose of this study is to determine which B lymphocytes subsets are responsible for the production of IgM, IgG2 and IgA anti-pneumococcal capsular polysaccharides after vaccination with a 23-valent pneumococcal polysaccharide vaccine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of this study is to identify which specific B cell subset(s) is/are responsible for the production of protective IgM, IgG2 and IgA anti-pneumococcal capsular polysaccharides (capPS) in response to immunization of healthy individuals with the Pneumovax, a prototypical T-independent type 2 vaccine. In other words, from which B cells are IgM, G2 and A-secreting plasma cells derived? To address this question, it will be taken advantage of the unique Ig heavy chain VDJ signature expressed by each B cell clone and the strategy will rely on the search of clonal filiations between plasmablasts (PB)/plasma cells (PC) and different B cell subpopulations. Therefore, healthy individuals will be vaccinated with Pneumovax, and blood samples will be collected at day 0, 7, 14, 28 and 56. Starting from these blood samples, different B cells subsets (in particular IgM+IgD+CD27+ and switched memory IgM-IgD-CD27+ B cells) and the PB/PC peaking at day 7 after vaccination will be isolated by cell sorting. CapPS-secreting PB cannot be specifically isolated, but the investigators assume that they will represent the majority of the isolated PB/PC at the peak of the response. Thus, day 7-PB/PC will be sorted both in bulk or as single cells in 96-well PCR plates. RNA will be extracted from bulk sorted PB/PC, and VDJ-µ, -alpha and -gamma Ig transcripts will be amplified by RT-PCR and analyzed by the H-CDR spectratyping method in order to identify the sequence of dominant VDJ signatures that most probably correspond to anti-capPS-secreting cells. In parallel, for each PB/PC single cell, Ig heavy and corresponding Ig light chain gene transcripts will be amplified by nested RT-PCR, sequenced, and provided that the heavy chain contains a dominant VDJ signature, they will be cloned into eukaryotic expression vectors to produce monoclonal human Abs. The recombinant antibodies will then be tested for reactivity against capPS from the vaccine by ELISA. When VDJ signatures of capPS will be validated, with this powerful molecular tool, the investigators will look for the presence of these signatures through VDJ-specific PCR on cDNA prepared from the different B cell subsets.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Centre d'Investigation Clinique, hôpital Necker Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • male
  • aged 18 to 40 y

Exclusion Criteria:

  • no documented primary immunodeficiency
  • no splenectomy
  • no functional/congenital asplenia,
  • no pneumococcal infections within the last 5 years before enrolment into the research protocol
  • no vaccinations with the 23-valent pneumococcal polysaccharide vaccine or the 7- or 13-valent conjugate-polysaccharide vaccines within the last 5 years before enrolment into the research protocol
  • no other vaccination within 1 month before enrolment into the research protocol
  • fever, current antibiotic treatment
  • any chronic or inflammatory disease
  • any immunosuppressive treatment
  • hyper-responsiveness to one component of the Pneumovax vaccine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: pneumovax
Single arm, open label pneumovax vaccination of healthy subjects
Drug: pneumovax vaccination
vaccination
Other Names:
  • pneumovax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the precursor of B lymphocytes
Time Frame: day 7
On vitro measure of blood mononuclear cell populations by cell sorting at day 7 to identify the clonal progeny of the secreting B lymphocyte precursor
day 7

Secondary Outcome Measures

Outcome Measure
Time Frame
measure of serum anti-capsular polysaccharide antibody titers
Time Frame: day 0, day 28
day 0, day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Study Director: Sandra WELLER, PhD, Institut National de la santé et de la recherché Médicale (INSERM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 18, 2014

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 5, 2016

Study Registration Dates

First Submitted

April 15, 2014

First Submitted That Met QC Criteria

April 29, 2014

First Posted (Estimated)

April 30, 2014

Study Record Updates

Last Update Posted (Estimated)

August 29, 2025

Last Update Submitted That Met QC Criteria

August 22, 2025

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INSERM-C12-10
  • 2013-000850-23 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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