Polysaccharide vaccines are a type of immunization developed to defend against bacteria with an outer shell, or capsule, made of sugar molecules called polysaccharides. This capsule acts as a defense mechanism, helping the bacteria hide from the body’s immune system. The vaccine introduces pieces of this capsule into the body, prompting an immune reaction that prepares the body to fight the actual bacteria. By using only a part of the bacterium, the vaccine provides this protection without causing illness.
How Polysaccharide Vaccines Stimulate Immunity
Certain bacteria, such as Streptococcus pneumoniae and Neisseria meningitidis, are difficult for the immune system to handle due to their polysaccharide capsules. The immune pathway activated by these vaccines is a T-cell-independent response, where the polysaccharide antigens directly interact with B-cells. The repetitive structure of the molecules allows them to bind to multiple receptors on a B-cell at once. This strong signal activates the B-cell directly, without requiring assistance from T-helper cells.
Once stimulated, B-cells mature into plasma cells that produce antibodies, primarily of the IgM class. These antibodies attach to the bacterial capsule, marking the pathogen for destruction. This response, however, does not generate strong immunological memory. Without T-cell involvement, the production of long-lived memory B-cells is limited, meaning protection may wane over time.
Limitations in Young Children
The T-cell-independent mechanism is the source of the vaccine’s primary limitation: it is not effective in infants and children under two years of age. Their developing immune systems cannot react effectively to polysaccharide antigens. This is because the specific B-cells responsible for the response, known as marginal zone B-cells, are not fully developed in the first few years of life.
These cells are located in the spleen and other lymphoid tissues and are specialized to react to T-cell-independent antigens. Without a mature population of these B-cells, an infant’s immune system cannot mount a reliable defense when given a pure polysaccharide vaccine. This results in a poor antibody response, affording little protection and prompting the development of a more advanced vaccine technology.
The Role of Conjugate Vaccines
To overcome the shortcomings in young children, scientists developed conjugate vaccines. This approach involves chemically linking the polysaccharide to a carrier protein the immune system can easily recognize, such as a harmless variant of the tetanus or diphtheria toxoid. The addition of the carrier protein changes how the immune system processes the antigen.
When a B-cell binds to the polysaccharide, it internalizes the entire complex and presents fragments of the carrier protein on its surface. This presentation attracts T-helper cells, transforming the immune reaction into a T-cell-dependent response. The T-cell provides secondary signals to the B-cell, stimulating a more potent and durable immune reaction.
This process leads to the production of high-affinity antibodies, primarily of the long-lasting IgG class, and the generation of memory B-cells. This immunological memory ensures long-term protection and a rapid response upon future exposure. This makes conjugate vaccines highly effective for infants and toddlers.
Diseases Targeted by Polysaccharide Vaccines
Both polysaccharide and conjugate vaccines are used to protect against the same types of encapsulated bacteria, but their application differs based on the target population. The primary diseases addressed include those caused by Streptococcus pneumoniae (pneumococcal disease), Neisseria meningitidis (meningococcal disease), and Haemophilus influenzae type b (Hib).
For pneumococcal disease, a pure polysaccharide vaccine known as Pneumovax 23 (PPSV23) is available. It covers 23 different strains of the bacteria and is recommended for adults 65 years or older and for younger adults with certain health conditions. In contrast, the Prevnar series (PCV13, PCV15, and PCV20) are conjugate vaccines and a standard part of the childhood immunization schedule because they are effective in infants.
A similar distinction exists for meningococcal vaccines. Polysaccharide versions (MPSV4) are available but are less commonly used now. Conjugate vaccines like Menactra, Menveo, and Bexsero are preferred for adolescents and infants, providing more durable protection. The development of the Hib conjugate vaccine was a major public health success, drastically reducing rates of meningitis and epiglottitis in children since its introduction into routine infant immunization schedules.