Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas

Abstract

Detoxified-lipooligosaccharide (dLOS)-protein conjugates from nontypeable Haemophilus influenzae (NTHi) elicited a significant rise of anti-LOS antibodies with bactericidal activity in rabbits (X.-X. Gu, C.-M. Tsai, T.

Protection against Development of Otitis Media Induced by NontypeableHaemophilus influenzaeby Both Active and Passive Immunization in a Chinchilla Model of Virus-Bacterium Superinfection

“…However, strain-specific bactericidal antibody does protect against OM (22). Thus, the bactericidal activity of immune serum may also have contributed to the clearance of NTHI seen here in the middle ears, since a correlation has been shown between the bactericidal activity of antibody directed against the HMW adhesin proteins (12), lipooligosaccharide (28) or polyribosyl ribitol phosphate-conjugated LPD and PDm (3) and protective efficacy in experimental models of human OM. However, anti-P6 antibodies with significant bactericidal activity have not been directly associated with clearance of NTHI from either the chinchilla nasopharynx (18) or the rat lung (42), although a predisposing viral infection was, again, not a component of either model.…”

“…Several outer membrane proteins of nontypeable Haemophilus influenzae (NTHI) as well as its lipooligosaccharide have been the subject of recent studies designed to assess their utility as potential immunogens against bacterial otitis media (OM) (3,12,13,18,26,28,30,34,37,44,53,66). The vast majority of these studies have been performed with chinchillas as the host and with disease induced by direct inoculation of the middle ear via transbullar challenge.…”

“…Several current candidate immunogens, which have been shown to reduce the incidence or severity or both of OM in the chinchilla or rat host are a mixture of rPCP, P4, and P6 (26); rHtrA (44); the high-molecular-weight (HMW) adhesin proteins (13); detoxified lipooligosaccharide-protein conjugates (28); outer membrane protein P6 (18); and lipoprotein D (LPD) (3,34). Our laboratory has similarly demonstrated that fimbrin, an NTHI adhesin (11,36,57,58) homologous to outer membrane protein P5 (66), can be used as a parenteral immunogen to significantly reduce the incidence and/or severity of OM in similar direct-challenge models.…”

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

“…Unlike H. influenzae type b, for which a highly successful vaccine is available, there is no vaccine against NTHi-induced diseases. Efforts to develop NTHi vaccines have been focused on surface antigens such as outer membrane proteins (OMP), pili/fimbriae, and lipooligosaccharide (LOS) (3,5,9,12,27,32). These antigens are believed to play an important role in the interaction of the bacteria with the hosts in vivo (23).…”

“…These antigens are believed to play an important role in the interaction of the bacteria with the hosts in vivo (23). OMP and LOS are two major surface antigens that are considered to be potential vaccine candidates because they induced bactericidal antibodies in humans (4,8) and conferred protection against experimental NTHi OM in animals (12,20), although both antigens showed antigenic variation among NTHi strains (26,29).…”