Vaccination to gain humoral immune memory

Abstract

The concept of immune memory forms the biological basis for vaccination programs. Despite advancements in the field of immune memory and vaccination, most current vaccines are evaluated by magnitude of antigen-specific antibody titers in serum or mucosa after vaccination. It has been shown, however, that antibody-mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, suggesting that assessment of vaccine efficacy should be performed for several years after vaccination. This long-term investigation is disadvantageous for prevalent and pandemic infections. Long-lived memory plasma cells and memory helper T cells which contribute to humoral immune memory are generated in the bone marrow after migration of memory cell precursors through bloodstream. Thus, it may be a novel evaluation strategy to assess the precursors of memory cells in the blood in the early phase of the immune reaction(s). We here review recent advances on the generation and maintenance of immune memory cells involved in humoral immunity and introduce a current concept of direct and short-term assessment of humoral immune memory formation upon vaccination as a correlate of protection.

Figure 1

Generation and maintenance of immune memory. During the course of an infection or immunization, antigen-incorporated dendritic cells prime naive CD4 T cells in SLOs. Within the pool of activated CD4 T cells, a small population of memory precursor cells preferentially migrate into the BM, further differentiate into memory Th cells and survive on VCAM-1⁺ collagen XI⁺ IL-7⁺ reticular stromal cells. The other small population of activated CD4 T cells interacts with bystander B cells as follow-on antigen-presenting cells through cognate interaction and further differentiates into effector Tfh cells. Some activated B cells differentiate into memory B cells and short-lived plasma cells. In the course of an antigen-persistent or recall response, memory B cells differentiate into plasma blasts including memory plasma cell precursors which eventually move to the BM in a CXCR4-CXCL12 dependent manner. BM reticular stromal cells expressing VCAM-1 and CXCL12 provide a niche for memory plasma cells. Additionally, megakaryocytes (MK) and eosinophils (Eos), both expressing the survival factors APRIL and IL-6, are in close vicinity to the memory plasma cell survival niche. PC: plasma cell.

Figure 2

The balance of splenic effector Tfh cells and BM memory Th cells is determined by the quantity and duration of antigen. By antigen persistence, the generation of BM resting memory cells is not affected, while the numbers of splenic effector Tfh cells are enhanced.