Characterisation of Human B Cell Maturation in Response to Vaccination

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.