BARENKAMP SJ; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 535.

Saint Louis Univ. Sch. of Med., Saint Louis, MO

BACKGROUND: The sera of children recovered from acute nontypable Haemophilus influenzae (NTHI) otitis media contain high levels of antibody against immunogenic surface-exposed high molecular weight (HMW) proteins. Methods andRESULTS: We cloned, expressed, and sequenced genes from a prototype NTHI strain that encode two such proteins, designated HMW1 and HMW2. Roughly 75% of NTHI express proteins of the HMW1/HMW2 family. Despite size heterogeneity, the HMW1/HMW2 proteins from different strains share common surface-accessible B cell epitopes. Furthermore, the HMW1/HMW2 proteins are critical adhesins, being required for attachment of NTHI to human epithelial cells in vitro. From the vaccine perspective, immunization of chinchillas with an HMW1/HMW2 mixture provided 50% complete protection against experimental otitis media caused by the homologous strain. Although infection developed in some animals, middle ear fluid bacterial densities were 50-fold lower than in controls. Infection in immunized animals was caused by bacteria down-regulated in HMW protein expression, suggesting bacterial selection in response to immunologic pressure. Of the 25% of NTHI that do not express HMW1/HMW2-like proteins, most still adhere to epithelial cells in vitro. We cloned, expressed, and sequenced a gene encoding a different class of HMW adhesin from a prototype HMW1/HMW2-deficient strain. This gene, designated hia (Haemophilus influenzae adhesin) is present and expressed in nearly all NTHI strains that are HMW1/HMW2-deficient. Conversely, strains that express HMW1/HMW2-like proteins lack expression of an Hia-like protein.CONCLUSIONS: Vaccines based upon a combination of HMW1/HMW2-like and Hia-like adhesins may have the potential to protect against otitis media caused by most or all NTHI.KEYWORDS: Haemophilus influenzae; Otitis media; Vaccine

Publication Types:

• Meeting Abstracts

Keywords:

• Adhesins, Bacterial
• Animals
• Bacterial Vaccines
• Base Sequence
• Child
• Chinchilla
• Ear, Middle
• Haemophilus Infections
• Haemophilus influenzae
• Humans
• Immunization
• In Vitro
• Molecular Weight
• Otitis Media
• Vaccines
• genetics
• growth & development
• immunology

Other ID:

• GWAIDS0011579

UI: 102249077

From Meeting Abstracts