Clinical Information

Streptococcus pneumoniae (S pneumoniae) is a gram-positive bacterium that causes a variety of infectious diseases in children and adults, including invasive disease (bacteriemia and meningitis) and infections of the respiratory tract (pneumonia and otitis media).(1) More than 90 serotypes of S pneumoniae have been identified, based on varying polysaccharides found in the bacterial cell wall. The serotypes responsible for disease vary with age and geographic location.

Bacterial polysaccharides induce a T-cell independent type II humoral immune response. In adults and older children, bacterial polysaccharides are effective in generating an immune response that results in production of IgG antibodies and generation of long-lived plasma cells and memory B cells.(2) S pneumoniae purified polysaccharide vaccines (PPSV) that contain a total of 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F) are available; these are referred to as PPSV23.(3) These 23 serotypes were included because, as a group, they account for approximately 90% of invasive pneumococcal infections. Antibody responses develop in approximately 75% to 85% of nonimmunocompromised adults and older children approximately 4 to 6 weeks following immunization with purified polysaccharide vaccines. A meta-analysis estimated an efficacy of 74% for prevention of invasive pneumococcal disease in adults vaccinated with PPSV23.(4) In contrast, immune responses to polysaccharide antigens in children younger than 2 years of age are generally weak.

Active immunization of children younger than 2 years requires vaccines prepared of polysaccharides conjugated to an immunogenic carrier protein (Corynebacterium diphtheria strain C7), which results in a T-cell dependent antibody response.(3) In children younger than age 6, prior to the availability of routine S pneumoniae vaccination, 7 serotypes (4, 6B, 9V, 18C, 19F, and 23F) accounted for 80% of invasive disease and up to 100% of all isolates that were found to be highly resistant to treatment with penicillin. The first pneumococcal conjugated vaccine (PCV) available for children younger than age 2 contained these 7 serotypes (PCV7). The vaccine was highly effective, with invasive disease in children younger than age 5 reduced from 99 to 21 cases per 100,000 population from 1998 to 2008.(5) In addition, it was demonstrated that after PCV7 became part of the routine vaccination schedule, only 2% of invasive disease was associated with any of the serotypes present in the vaccine. Instead, approximately 61% of the invasive disease was caused by an additional 6 serotypes (1, 3, 5, 6A, 7F, and 19A). This led to development of a 13-valent conjugated vaccine, known as PCV13. More recently, additional pneumococcal conjugate vaccines have been approved, specifically 15-valent (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F) and 20-valent (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F) vaccines, known as PCV15 and PCV20, respectively.

Conjugated pneumococcal vaccination is included in the routine childhood schedule, with 4 doses of PCV13 or PCV15 administered at 2, 4, 6, and 12 to 15 months.(6) For adults younger than 65 years, a single dose of PCV20 or a single dose of PCV15 followed 1 year later with a single dose of PPSV23 is recommended.(7) This same pneumococcal vaccination strategy is recommended for adults 19 to 64 years of age with immunocompromising conditions, cochlear implants, cerebrospinal fluid leaks, or other chronic health conditions.

Patients with intrinsic defects in humoral immunity, such as common variable immunodeficiency, may have impaired antibody responses to pneumococcal vaccination.(8,9) Selective antibody deficiency is a recognized clinical entity in patients older than 2 years of age and is characterized by recurrent bacterial respiratory infections, absent or subnormal antibody response to a majority of polysaccharide antigens, and normal or increased immunoglobulin concentrations, including IgG subclasses, in the context of intact humoral response to protein antigens. In several other primary immunodeficiencies, including Wiskott-Aldrich syndrome, autoimmune lymphoproliferate syndrome, and DiGeorge syndrome, IgG subclass deficiencies may also result in impaired antibody responses to polysaccharide antigens.