Characterisation of Human B Cell Maturation in Response to Vaccination

Hepatitis B Clinical Trial

— BVAC  

Official title:

Characterisation of Human B Cell Maturation in Response to Vaccination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03535779
• Other study ID #: 16SM3542
• Status: Completed
• Start date: March 6, 2017
• Est. completion date: March 13, 2018

Study information

• Verified date: June 2018
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study is an exploratory single site sample collection study at St Mary's hospital campus, Imperial College London. Sixteen participants scheduled to receive routine immunizations for Td/IPV (group 1) and HBsAg (group 2) will be recruited overall. Eights participants will be allocated to group 1 and eights participants to group 2 depending on their immunisation regime.

Description:

The aim of the study is to characterise the maturation of human B cell response to immunization with vaccines (HBsAg and Td/IPV) known to induce long-term memory responses.

The primary objective is to characterize the number and phenotype of memory B cells induced by routine vaccination. These responses will be used as a comparison to those currently induced in HIV-1 vaccination trials.

The development of an effective HIV-1 vaccine is highly dependent on our understanding of the immune response to HIV-1 infection/vaccination. It is generally accepted that the generation of long-lived neutralising memory B cell antibody responses will be critical for an effective vaccine against HIV-1. Successful vaccines are capable of inducing long-lived B cell memory that can maintain antibodies for decades, typical examples being those induced by Hepatitis B (HBsAg) and tetanus vaccination which generates antibodies with a half-life of greater than 5 years. In contrast, current HIV-1 vaccination typically induces a short-lived B cell response with antibodies waning within a half-life of 6 months. Recent observations have shown that vaccination does not produce a homogenous population of memory B cell but rather a constellation of subsets depending on the type of vaccination.

Investigators are only beginning to understand the varying and important roles of some of these elusive subsets. Therefore understanding potential differential responses of these memory B cell subsets to successful licensed vaccines may prove critical in the creation of novel, effective vaccines to HIV-1.

The field has been energised in recent years by the identification of different memory B cell subsets. Four of these subsets can be characterised through differential expression of surface markers CD27, IgD and IgM, typically: CD27+IgD+IgM+ B cells, CD27+IgD-IgM+ B cells, CD27+IgD+IgM- B cells and CD27+IgD-IgM- IgG+/IgA+/IgE+ B cells (Mroczek ES et al, Front Immunol. 2014;5:96). Understanding how HBsAg and tetanus (as part of the Td/IPV vaccine) modulates antigen specific responses across these four memory B cell subsets will help define how Investigators understand the establishment of long-term immunological memory and may help us understand how Investigators can induce such memory responses with new HIV vaccine candidates. Data from these studies will be used to compare responses elicited by HIV vaccines in current phase I studies and determine potential defects in the maturation of vaccine induced memory.

Investigators therefore wish to obtain blood draws from individuals undergoing routine HBsAg and Td/IPV vaccination. This will allow us to isolate memory B cells circulating in the peripheral blood and characterise the different memory B cell subsets induced by effective licensed vaccines and compare responses to those induced by current HIV-1 vaccination trials, for which Investigators already have samples banked.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 13, 2018
• Est. primary completion date: June 15, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy male and female volunteers aged between 18 and 55 years scheduled to receive routine vaccination for HBsAg or booster immunisation with Td/IPV

2. Previously naïve to HBsAg vaccination

3. Available for the duration of the study

4. Willing and able to give written informed consent

Exclusion Criteria:

1. Is currently participating in another clinical trial with an investigational or non-investigational drug or device

2. Unable to read and/or speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent

3. Unlikely to comply with protocol

4. Has a condition which in the opinion of the investigator is not suitable for participation in the trial

Related Conditions & MeSH terms

• Hepatitis B

Intervention

Biological:
• Hepatitis B
The Hepatitis B virus, is a double stranded DNA virus that prevents Hepatitis B in the population
• Tetanus Toxoid
The Tetanus vaccine, also known as tetanus toxoid (Td/IVP), is an inactive vaccine used to prevent tetanus in the population

Locations

Country	Name	City	State
United Kingdom	Dr Lucy Garvey	Paddington

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Memory B Cells	The primary endpoint will measure the proportion responding B cells in one of four memory B cell subsets (defined by differential expression of CD27, IgD and IgM markers) raised in response to HBsAg and Td/IPV vaccination.	12 months