Significant variation in serotype-specific immunogenicity of the seven-valent Streptococcus pneumoniae capsular polysaccharide-CRM197 conjugate vaccine occurs despite vigorous T cell help induced by the carrier protein.
Streptococcus pneumoniae capsular polysaccharides (PnPSs) induce protective antibodies but are T cell-independent type 2 antigens and are poorly immunogenic in infants. Conjugate vaccines of PnPSs linked to proteins like cross-reactive material (CRM(197)) increase PS antibody titer and elicit immunologic memory in infants. Despite being linked to an identical carrier protein, each PS component of the 7-valent PnPS-CRM(197) vaccine has different immunogenicity. To determine whether variations in conjugate-induced memory T cell responses or PnPS-specific antibody-secreting cells (ASCs) were responsible for serotype-specific differences in immunogenicity, adults were immunized with 7-valent PnPS-CRM(197), and antibody titer, vaccine component-specific CD4(+) T cell recall response, numbers of PnPS-specific ASCs, and cytokine production were measured. PnPS-CRM(197) induced significantly different serotype-specific antibody titers, despite vigorous T cell recall responses to all 7 vaccine components, and production of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon-gamma. We conclude that PnPS-CRM(197) induces variable serotype-specific antibody titers, despite induction of comparable CRM(197)-specific memory T cell responses.
Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA.
Kulwant K
KK
Kamboj
H Lester
HL
Kirchner
Rhonda
R
Kimmel
Neil S
NS
Greenspan
John R
JR
Schreiber
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D022242:Pneumococcal Vaccines / Q000276:immunology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)