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Infect Immun, May 1998, p. 1891-1897, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Synthesis and Characterization of Lipooligosaccharide-Based Conjugates as Vaccine Candidates for Moraxella (Branhamella) catarrhalis

Xin-Xing Gu,1,* Jing Chen,1 Stephen J. Barenkamp,2 John B. Robbins,3 Chao-Ming Tsai,4 David J. Lim,5 and James Battey1

Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 208501; Department of Pediatrics, St. Louis University School of Medicine, St. Louis, Missouri 631042; National Institute of Child Health and Development3 and Food and Drug Administration,4 Bethesda, Maryland 20892; and House Ear Institute, Los Angeles, California 900575

Received 20 November 1997/Returned for modification 8 January 1998/Accepted 11 February 1998

Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases.

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

Infect Immun, May 1998, p. 1891-1897, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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