Clinical Information

Streptococcus pneumoniae is a gram-positive bacteria that causes a variety of infectious diseases in children and adults, including invasive disease (bacteremia and meningitis) and infections of the respiratory tract (pneumonia and otitis media).(1,2) In 2009, it is estimated that S pneumoniae was responsible for approximately 43,500 infections and 5,000 deaths in the United States. More than 90 serotypes of S pneumoniae have been identified, based on varying polysaccharides that are 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. Vaccines containing bacterial polysaccharides can be effective in generating an immune response that results in production of IgG antibodies and generation of long-lived plasma and memory B cells, which can protect an individual against bacterial disease. Active immunization of adults and children older than 2 years is performed with nonconjugated polysaccharide vaccines (Pneumovax and Pnu-Immune 23) that contain a total of 23 serotypes, namely 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.(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. Immunization with a 23-valent vaccine is recommended for all adults 65 years of age and older, and for adults 18 to 64 years of age with certain chronic diseases (heart disease, lung disease, type I diabetes, liver disease), those who are immunocompromised (congenital or acquired immunodeficiencies, malignancy, solid-organ transplant), and those with functional or anatomic asplenia.(3) 

In contrast to adults and older pediatrics, 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 multiple injections of vaccine prepared from purified polysaccharides conjugated to an immunogenic carrier (Corynebacterium diphtheria strain C7 protein), which results in a T-cell dependent antibody response. 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 conjugated vaccine available for children younger than age 2 (Prevnar) contained these 7 serotypes.(4,5) 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. In addition, it was demonstrated that after Prevnar became part of the routine vaccination schedule, only 2% of invasive disease was associated with any of the serotypes present in the 7-valent conjugate vaccine. Instead, approximately 61% of the invasive disease was caused by an additional 6 serotypes, including 1, 3, 5, 6A, 7F, and 19A. This led to development of a 13-valent S pneumoniae polysaccharide conjugate vaccine, which is marketed as Prevnar13. Prevnar13 is approved for administration to all children ages 6 weeks to 71 months, and has replaced the previous 7-valent Prevnar vaccine.(6)

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