Vaccine Immunology - Clinical Tree

Generating vaccine-mediated protection is a complex challenge. Up to the year 2000, vaccines have largely been developed empirically, with little or no understanding of how they activate the immune system. Subsequently, the antigens to be included in vaccines such as meningococcal group B, subunit zoster, RTS/S malaria, human papillomavirus (HPV), and SARS-CoV-2 vaccines were defined based on their biological importance and presented in various ways to elicit the presumed correlate of protection. The early protective efficacy of vaccines is primarily conferred by the induction of antigen-specific antibodies ( Box 2.1 ). However, there is more to antibody-mediated protection than the peak of vaccine-induced antibody levels. The quality of such antibodies (e.g., their avidity, specificity, or neutralizing capacity) has been identified as a determining factor in efficacy. Long-term protection requires the persistence of vaccine antibodies above protective thresholds and/or the maintenance of immune memory cells capable of rapid and effective reactivation with subsequent microbial exposure. The determinants of immune memory induction, as well as the relative contribution of persisting antibodies and of immune memory to protection against specific diseases, are essential parameters of long-term vaccine efficacy.

BOX 2.1

Main Immunological Definitions

ADJUVANT

Agents that increase the stimulation of the immune system by enhancing antigen presentation (depot formulation, delivery systems) and/or by providing costimulatory signals (immunomodulators). Aluminum salts are most often used in today’s vaccines.

AFFINITY, AVIDITY

Antibody affinity refers to the tendency of an antibody to bind to a specific epitope at the surface of an antigen; that is, to the strength of the interaction. Avidity is the sum of the epitope-specific affinities for a given antigen. It directly relates to its function.

AFFINITY MATURATION

Processes through which antigen-specific B cells undergo somatic hypermutation and affinity-based selection, resulting in B cells that produce antibodies with increased affinity over germline antibodies.

ANTIBODIES

Proteins of the immunoglobulin family, present on the surface of B lymphocytes, secreted in response to stimulation, that neutralize antigens by binding specifically to their surface.

ANTIGEN-PRESENTING CELLS

Cells that capture antigens by endocytosis or phagocytosis, process them into small peptides, display them at their surface through major histocompatibility complex (MHC) molecules, and provide costimulatory signals that act synergistically to activate antigen-specific T cells. Antigen-presenting cells include B cells, macrophages, and dendritic cells, although only dendritic cells are capable of activating naïve T cells.

B LYMPHOCYTES

Cells that originate in the bone marrow, mature in secondary lymphoid tissues, become activated in the spleen/lymph nodes when their surface immunoglobulins bind to an antigen, and differentiate into antibody-secreting cells (plasma cells) or memory B cells.

CARRIER PROTEIN

A protein that is used as a template to which polysaccharide moieties are chemically conjugated to generate glycoconjugate vaccines. It is believed that carrier proteins provide antigenic epitopes for recognition by CD4 ⁺ T-helper cells, in particular follicular T-helper cells.

CD4 ⁺ T-HELPER 1 LYMPHOCYTES

CD4 ⁺ T cells that on activation differentiate into cells that mainly secrete interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-β, exerting direct antimicrobial functions (viruses), and essentially providing support to cytotoxic T cells and macrophages.

CD4 ⁺ T-HELPER 2 LYMPHOCYTES

CD4 ⁺ T cells that on activation differentiate into cells that mainly secrete IL-4, IL-5, IL-6, IL-10, and IL-13, exerting direct antimicrobial functions (parasites) and essentially providing support to B lymphocytes.

CD4 ⁺ T-HELPER 17 LYMPHOCYTES

CD4 ⁺ T cells that mainly secrete IL-17, IL-21, and IL-22 and are implicated in host defense against extracellular bacteria colonizing exposed surfaces (airways, skin, gut).

CD8 ⁺ T CELLS

Lymphocytes that specialize in the killing of infected cells, through direct contact or cytokine (IFN-γ, TNF-α) production.

CENTRAL MEMORY T CELLS

Memory T cells traffic through the lymph nodes, ready to proliferate and generate a high number of effector cells in response to specific microbial peptides.

CHEMOKINES

Small secreted proteins that function as chemoattractants, recruiting cells that express the corresponding chemokine receptors at their surface and thus migrating toward higher concentrations of chemokines.

COSTIMULATORY MOLECULES

Molecules that become expressed at the surface of antigen-presenting cells on activation and deliver stimulatory signals to other cells, namely T and B cells.

DENDRITIC CELLS

Cells that constantly sample their surroundings for pathogens such as viruses and bacteria, detect danger, and initiate immune responses. Immature patrolling dendritic cells (DCs) have high endocytic activity and a low T-cell activation potential. Contact with a pathogen induces maturation and the expression of certain cell-surface molecules, greatly enhancing their ability to activate T cells.

EFFECTOR MEMORY T CELLS

Memory T cells patrol through the body to detect specific microbial peptides and are capable of an immediate cytotoxic function in case of recognition.

EXTRAFOLLICULAR REACTION

B-cell differentiation pathways that occur outside of germinal centers in response to protein or polysaccharide antigens. Extrafollicular reaction is rapid, generates B cells that are short-lived (days), and produces low-affinity antibodies without inducing immune memory.

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