Characterisation of Human B Cell Maturation in Response to Vaccination
Condition: Hepatitis B
MeSH terms: Hepatitis B
Study type: Observational [Patient Registry]

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.
    

Detailed 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.
    

Intervention name(s): Hepatitis B; Tetanus Toxoid
Intervention type(s): Biological; Biological
Intervention description(s): The Hepatitis B virus, is a double stranded DNA virus that prevents Hepatitis B in the population; The Tetanus vaccine, also known as tetanus toxoid (Td/IVP), is an inactive vaccine used to prevent tetanus in the population
Other intervention name(s): HBsAg; Td/IVP
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy and male and female volunteers aged between 18 and 55 years old.