Codelivery of adjuvants at the primary immunization site is essential for evoking a robust immune response to neoglycoconjugates.
A series of nonformulated adjuvants, i.e. Quil-A, MPL, DDA, CpG and Alum were codelivered with a synthetic branched tetrasaccharide fragment corresponding to Streptococcus pneumoniae type 14 polysaccharide (Pn14PS) conjugated to CRM(197) in order to investigate antibody- and cell-mediated immune responses in a mouse model. The first immunization was performed intracutaneously in the presence of adjuvants. Booster injections which were given without adjuvant dramatically enhanced and expanded the immune response from IgM to IgG1 and other IgG subclasses. Codelivery of the neoglycoconjugate with CpG or Alum had no additional effect over vaccine in saline, and elicited mainly IgG1 antibodies against Pn14PS. CpG even has a modest suppressive effect on the antibody response. Codelivery of the neoglycoconjugate with Quil-A, MPL, DDA alone or in combination resulted in both IgG1, IgG2a, IgG2b and IgG3 antibodies. Quil-A alone or in combination with MPL induced systemic IL-5 and IL-6 6h after primary immunization. This adjuvant combination also increased CD4/CD8 T cells ratio in lymph nodes and peripheral blood on day 1 after immunization. Seven days later, the ratios in blood and lymph nodes had returned to normal. In conclusion, codelivery of Quil-A alone or in combination with MPL had the most dramatic effect on antibody- and cell-mediated immune response to neoglycoconjugate of Pn14PS.
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Dodi
D
Safari
Huberta A Th
HA
Dekker
Ger
G
Rijkers
Harm
H
Snippe
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D001769:Blood / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005260:Female; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C092298:pneumococcal polysaccharide 14 - CRM 197