lipid-a and Haemophilus-Infections

Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is Gram-negative bacteria that are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A (MPL), a toll-like receptor (TLR) 4 agonist, as an adjuvant to induce mucosal immune responses against NTHi to enhance bacterial clearance from the nasopharynx.. Mice were administered 10 μg outer membrane protein (OMP) from NTHi and 0, 10, or 20 μg MPL intranasally once a week for 3 weeks. Control mice were administered phosphate-buffered saline alone. After immunization, these mice were challenged with NTHi. At 6 and 12 h after bacterial challenge, the mice were killed and nasal washes and sera were collected. The numbers of NTHi- and OMP-specific antibodies were quantified by enzyme-linked immunosorbent assay.. The MPL 10 and 20 μg group produced a significant reduction in the number of bacteria recovered from the nasopharynx at 12 h after bacterial challenge compared to the control group. OMP-specific IgA titers were also augmented in the MPL groups compared to the control and OMP groups.. MPL is suitable for eliciting effective mucosal immune responses against NTHi in the nasopharynx. These results demonstrate the possibility of an adjuvant that involves stimulation of the innate immune system by TLR4 agonists such as MPL for mucosal vaccination.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Bacterial; Enzyme-Linked Immunosorbent Assay; Female; Haemophilus Infections; Haemophilus influenzae; Immunity, Mucosal; Immunization; Lipid A; Mice; Mice, Inbred BALB C; Otitis Media

Immunogenicity of the lipid A component of Haemophilus somnus lipooligosaccharide in cattle and mice was examined after purification, detoxification, and covalent conjugation to a protein carrier. After 2 inoculations, a substantial antibody response was induced in most cattle to lipid A and the protein carrier. To determine whether antibodies to lipid A would be protective, 5 x 10(7) colony-forming units of H somnus strain 649 were administered IV to endotoxin-responsive (C3H/HeN) mice. In one study, 8 of 13 C3H/HeN mice aborted when inoculated. In contrast, abortion did not result when mice were inoculated with the same dose of an isolate of H somnus normally found in the prepuce or with the rough mutant Escherichia coli J5. In addition, endotoxin-nonresponsive (C3H/HeJ) mice were significantly (P = 0.03) more resistant to abortion by strain 649 than were C3H/HeN mice, but inoculated C3H/HeN mice were only slightly more resistant to H somnus abortion, compared with control mice. Although a large antibody response to lipid A was detected, there was no significant difference in the immunized group between mice that aborted and mice that delivered normally. Thus, lipooligosaccharide and other properties of virulent H somnus strains may contribute to abortion in mice.

Topics: Abortion, Veterinary; Animals; Antibodies, Bacterial; Bacterial Vaccines; Cattle; Cattle Diseases; Cricetinae; Disease Models, Animal; Female; Haemophilus; Haemophilus Infections; Hemocyanins; Lipid A; Mesocricetus; Mice; Mice, Inbred C3H; Ovalbumin; Pregnancy; Rats; Rats, Inbred Strains; Vaccines, Synthetic