Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals. Streptococcus pneumoniae (the pneumococcus) is a major cause of life-threatening invasive infections accounting for considerable morbidity and mortality worldwide (1). Children and adults with certain medical conditions as well as the elderly are at increased risk for invasive pneumococcal disease (IPD) and pneumonia, with disease rates up to 20 times higher than those in the general population (2). High-risk groups consist of children and adults with chronic diseases and with primary and secondary immune deficiencies and of persons with functional or anatomical asplenia. Persons older than 65 years of age are also at increased risk for pneumococcal infection, due to attenuation of their immune response caused by advancing age, a phenomenon called immunosenescence (3). The number of patients in need for protection against IPD is continually increasing due to rising numbers of people with chronic disease or HIV infection and an aging population in many high-income countries.Pneumococcal disease is usually more severe in such high-risk individuals than in immunocompetent subjects (4-6). While antibiotic resistance represents an additional hurdle for the successful treatment of pneumococcal infections (7, 8), optimal protection of such "high-risk" groups against S. pneumoniae infection through vaccination continues to be an important priority.For more than 2 decades, a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been recommended for the protection of immunocompromised individuals and the elderly against invasive pneumococcal disease (IPD) and pneumonia (9).The licensure of the pneumococcal polysaccharide vaccine (PPV) was based on trials of a 6-valent ...

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Current guidelines recommend a combined schedule of a 13-valent pneumococcal conjugate vaccine (PCV13) and PPSV23 (23-valent polysaccharide vaccine) for asplenic individuals. We show that PCV13 induces a T-dependent immune response in asplenic individuals with β-thalassemia, but previous PPSV23s affect the memory B-cell response in a dose- and time-dependent manner. Clinical Trials Registration. NCT01846923.

Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a major cause of morbidity and mortality worldwide. Achieving long-term immunity against S. pneumoniae through immunization is an important public health priority. Long-term protection after immunization is thought to rely both on protective serum antibody levels and immunological memory in the form of antigen-specific memory B cells (MBCs). Although the ability to achieve protective antibody levels shortly after pneumococcal vaccination has been well documented for the various infant immunization schedules currently in use worldwide, the examination of immunological memory in the form of antigen-specific MBCs has been much more limited. Such responses are critical for long-term protection against pneumococcal colonization and disease. This review summarizes the published literature on the MBC response to primary or booster immunization with either pneumococcal polysaccharide vaccine (PPV23) or pneumococcal conjugate vaccines (PCVs), aiming to elucidate the immunological mechanisms that determine the magnitude and longevity of vaccine protection against pneumococcus. There is evidence that PCVs induce the production of antigen-specific MBCs, whereas immunization with PPV23 does not result in the formation of MBCs. Increased understanding of the immunological factors that facilitate the induction, maintenance and recall of MBCs in response to pneumococcal vaccination could enable the use of MBC enumeration as novel correlates of protection against S. pneumoniae. Ongoing studies that examine MBC response to pneumococcal vaccination in high burden settings will be extremely important in our understanding of long-term protection induced by pneumococcal conjugate vaccines.