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Infection and Immunity, October 1999, p. 5508-5513, Vol. 67, No. 10
0019-9567/99/$04.00+0

Outer Membrane Proteins as a Carrier for Detoxified Lipooligosaccharide Conjugate Vaccines for Nontypeable Haemophilus influenzae

Ting-Huai Wu and Xin-Xing Gu*

Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850

Received 18 May 1999/Returned for modification 22 June 1999/Accepted 22 July 1999

Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines.

* Corresponding author. Mailing address: NIDCD, NIH, 5 Research Court, 2A31, Rockville, MD 20850. Phone: (301) 402-2581. Fax: (301) 402-4200. E-mail: guxx{at}nidcd.nih.gov.

Infection and Immunity, October 1999, p. 5508-5513, Vol. 67, No. 10
0019-9567/99/$04.00+0


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