Biomaterial Database

Antibody responses in serum and lung to intranasal immunization with Haemophilus influenzae type b polysaccharide conjugated to cholera toxin B subunit and tetanus toxoid. 1998

C Bergquist, and T Lagergård, and J Holmgren

Department of Medical Microbiology and Immunology, Göteborg University, Sweden.

OBJECTIVE Cholera toxin B subunit (CTB) has previously been used as a mucosal carrier for various vaccine candidate antigens. The objective of this study was to see if coupling a bacterial polysaccharide, Haemophilus influenzae type b capsular polysaccharide (HibCPS), to CTB, either directly or through prior coupling to tetanus toxoid (TT), would improve the immunogenicity of HibCPS after nasal immunization. METHODS HibCPS was conjugated to CTB, TT or via TT to CTB, using glutaraldehyde or 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDAC) and N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The conjugates were characterized and used for intranasal (IN) and subcutaneous (SC) immunizations of mice. The anti-Hib, -TT and -CTB antibody titers in serum and lungs after the immunizations were measured with ELISA. RESULTS The HibCTB was poorly immunogenic both given IN and SC compared with HibTT and HibTTCTB, probably because of inefficient coupling. In contrast, the conjugation of CTB to the HibTT conjugate resulted in a preparation which was superior both to the HibTT and the HibCTB conjugates in inducing local IgA and IgG anti-HibCPS antibodies in the lungs. The anti-HibCPS serum IgG titers after IN immunization with the HibTTCTB conjugate were similar to the titers after IN immunization with HibTT, or SC immunization with a commercial HibCRM conjugate vaccine. In contrast to the other conjugates, the HibTTCTB conjugate also gave rise to anti-Hib serum IgA titers. CONCLUSIONS We conclude that appropriate conjugation to CTB increases the mucosal immunogenicity of HibCPS, and that intranasal immunization with such a conjugate can give rise to both local and systemic anti-HibCPS antibody responses.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011135	Polysaccharides, Bacterial	Polysaccharides found in bacteria and in capsules thereof.	Bacterial Polysaccharides
D002772	Cholera Toxin	An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.	Cholera Toxin A,Cholera Toxin B,Cholera Toxin Protomer A,Cholera Toxin Protomer B,Cholera Toxin Subunit A,Cholera Toxin Subunit B,Choleragen,Choleragenoid,Cholera Enterotoxin CT,Cholera Exotoxin,Cholera Toxin A Subunit,Cholera Toxin B Subunit,Procholeragenoid,Enterotoxin CT, Cholera,Exotoxin, Cholera,Toxin A, Cholera,Toxin B, Cholera,Toxin, Cholera
D005260	Female		Females
D006192	Haemophilus Infections	Infections with bacteria of the genus HAEMOPHILUS.	Hemophilus Infections,Haemophilus influenzae Infection,Haemophilus influenzae Type b Infection,Hib Infection,Infections, Haemophilus,Infections, Hemophilus,Haemophilus Infection,Haemophilus influenzae Infections,Hemophilus Infection,Hib Infections,Infection, Haemophilus,Infection, Haemophilus influenzae,Infection, Hemophilus,Infection, Hib
D000281	Administration, Intranasal	Delivery of medications through the nasal mucosa.	Drug Administration, Intranasal,Administration, Intranasal Drug,Administration, Nasal,Intranasal Administration,Intranasal Drug Administration,Administrations, Intranasal,Administrations, Intranasal Drug,Administrations, Nasal,Drug Administrations, Intranasal,Intranasal Administrations,Intranasal Drug Administrations,Nasal Administration,Nasal Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000907	Antibodies, Bacterial	Immunoglobulins produced in a response to BACTERIAL ANTIGENS.	Bacterial Antibodies
D013745	Tetanus Toxoid		Tetanus Vaccine,Toxoid, Tetanus,Vaccine, Tetanus