Pneumococcal Conjugate and Plain Polysaccharide Vaccines Have Divergent Effects on Antigen-Specific B Cells

Abstract

Background. A 23-valent unconjugated pneumococcal polysaccharide vaccine (23vP), routinely administered at the age of 65, has limited effectiveness, and revaccination induces attenuated antibody responses. It is not known whether pneumococcal polysaccharide-protein conjugated vaccines (PCV), although highly effective in infants, offer any immunological advantages over 23vP in adults.Methods. We immunized adults with schedules combining both PCV and 23vP and investigated B-cell responses to establish whether PCV7 (a 7-valent PCV) induced T-dependent responses in adults, to assess the role of memory B cells in 23vP-induced antibody hyporesponsiveness, and to identify the B-cell subtypes involved.Results. A single dose of PCV7 induced significant increases in serotype-specific memory B-cell populations in peripheral blood indicating a T-dependent response. Conversely, immunization with 23vP resulted in a decrease in memory B-cell frequency. Furthermore, memory B-cell responses to subsequent immunization with PCV7, when given after 23vP, were attenuated. Notably, B1b cells, a subset important in protecting mice against pneumococci, were also depleted following immunization with 23vP in humans.Conclusions. This study indicates that PCV7 may have an immunological advantage over 23vP in adults and that 23vP-induced depletion of memory and B1b-cell subsets may provide a basis for antibody hyporesponsiveness and the limited effectiveness of 23vP.Clinical Trials Registration. ISRCTN: 78768849.

Polysaccharide-specific B cell responses to vaccination in humans

“…25 This may be because the polysaccharide quantity of each serotype is more than 10 times higher in the PPV-23 compared with the PCV-7 or may result from unconjugated polysaccharide antigens inducing the terminal differentiation of B MEM into PCs, a phenomenon which will be covered in more detail in the discussion of B MEM responses below.…”

“…34 In an adult study, vaccination with PCV-7 resulted in an increase in polysaccharide-specific B MEM whereas vaccination with PPV-23 had the opposite effect, causing a reduction in B MEM frequency. 25 Adults over the age of 65 are the only population to routinely receive PPV-23. This vaccine appears to offer a degree of short-term protection against invasive pneumococcal disease, 35 but no reduction in rates of pneumonia or mortality.…”

“…13 Hyporesponsiveness may be explained by the effect of polysaccharide vaccines on the B MEM population. Plain polysaccharide vaccines are thought to deplete the B MEM pool by inducing strong BCR cross-linking and driving the terminal differentiation of these cells into PCs, 25 or by inducing apoptosis as demonstrated in neonatal mice primed with MenCCV and boosted with MenCPS. 40 A recent study identified IgM-producing B cells as an important subset in the response to PPV-23 in young adults.…”

B Cell Memory to a Serogroup C Meningococcal Conjugate Vaccine in Childhood and Response to Booster: Little Association with Serum IgG Antibody

“…In addition, infants respond poorly to immunization with pure polysaccharide vaccines (T-independent Ags). Vaccination may induce tolerance or hyporesponsiveness to further doses rather than prime for a secondary response (50).…”

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine compared to the 23-valent pneumococcal polysaccharide vaccine in elderly Japanese adults

“…6 Protein conjugated vaccines such as PCV13 are thought to have immunologic advantages over free polysaccharide pneumococcal vaccines. 9 By conjugating the capsular polysaccharide to a carrier protein (CRM 197 ), PCV13 elicits memory B cells indicating a T cell-dependent response. 9,10 Immunologic memory on subsequent natural exposure or revaccination may sustain PCV13 protective antibody responses.…”