Claims

1. A vaccine formulation comprising an active ingredient selected from the group consisting of an htrB mutant of a gram-negative bacterial pathogen, endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen, endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen said endotoxin conjugated to a carrier protein, and an htrB mutant of said gram-negative bacterial pathogen which has been genetically engineered to express at least one heterologous vaccine antigen; wherein said htrB mutant lacks one or more secondary acyl chains of lipid A contained in the gram-negative bacterial pathogen resulting in substantially reduced toxicity when compared to lipid A of the gram-negative bacterial pathogen.

2. The vaccine formulation of claim 1, wherein the active ingredient consists essentially of an htrB mutant of said gram-negative bacterial pathogen.

3. The vaccine formulation of claim 1, wherein the active ingredient consists essentially of endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen.

4. The vaccine formulation of claim 1, wherein the active ingredient consists essentially of endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen, wherein the isolated endotoxin is conjugated to a carrier protein.

5. The vaccine formulation of claim 1, wherein the active ingredient consists essentially of an htrB mutant of said gram-negative bacterial pathogen which has been genetically engineered to express at least one heterologous antigen from a microbial pathogen.

6. The vaccine formulation of claim 1, further comprising a physiological carrier and an adjuvant.

7. The vaccine formulation of claim 1, wherein the gram-negative bacterial pathogen is a Neisseria, Haemophilus, Moraxella, Campylobacter, Salmonella, Shigella, or Pseudomonas gram-negative bacterial pathogen.

8. The vaccine formulation of claim 7, wherein the gram-negative bacterial pathogen is Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Haemophilus ducreyi, Moraxella catarrhalis, Campylobacter jejuni, Salmonella typhimurium, Shigella dysentariae, or Pseudomonas aeruginosa.

9. The vaccine formulation of claim 8, wherein the gram-negative bacterial pathogen is Haemophilus influenzae.

10. The vaccine formulation of claim 9, wherein the gram-negative bacterial pathogen is non-typeable Haemophilus influenzae.

11. The vaccine formulation of claim 10, wherein the endotoxin of the htrB mutant contains a decreased phosphoethanolamine content and an increased hexose content in the mutant endotoxin's inner core, and a pentaacylated or tetraacylated lipid A lacking one or two secondary acyl chains compared to the corresponding wild-type non-typeable Haemophilus influenzae hexaacylated endotoxin.

12. A method for immunizing an individual to prevent disease caused by a gram-negative bacterial pathogen, the method comprising vaccinating the individual with a prophylactically effective amount of the vaccine formulation of claim 1.

13. The method of claim 12, wherein the individual is a human.

14. The method of claim 12, wherein the individual is not a human.

15. The method of claim 12, wherein the vaccine formulation is introduced by a route of administration selected from the group consisting of intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, ocular, intranasal, and oral administration.

16. The method of claim 12, wherein the vaccine formulation comprises an active ingredient consisting essentially of an htrB mutant of said gram-negative bacterial pathogen.

17. The method of claim 12, wherein the vaccine formulation comprises an active ingredient consisting essentially of endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen.

18. The method of claim 12, wherein the vaccine formulation comprises an active ingredient consisting essentially of endotoxin isolated from the htrB mutant of said gram-negative bacterial pathogen, wherein the isolated endotoxin is conjugated to a carrier protein.

19. The method of claim 12, wherein the vaccine formulation comprises an active ingredient consisting essentially of an htrB mutant of said gram-negative bacterial pathogen which has been genetically engineered to express at least one heterologous antigen from a microbial pathogen.

20. The method of claim 12, wherein the vaccine formulation further comprises a physiological carrier and an adjuvant.

21. The method of claim 15, wherein the vaccine formulation is administered orally as an additive to the individual's feed.

22. The method of claim 12, wherein the gram-negative bacterial pathogen is a Neisseria, Haemophilus, Moraxella, Campylobacter, Salmonella, Shigella, or Pseudomonas gram-negative bacterial pathogen.

23. The method of claim 22, wherein the gram-negative bacterial pathogen is Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Haemophilus ducreyi, Moraxella catarrhalis, Campylobacter jejuni, Salmonella typhimurium, Shigella dysentariae, or Pseudomonas aeruginosa.

24. The method of claim 23, wherein the gram-negative bacterial pathogen is Haemophilus influenzae.

25. The method of claim 24, wherein the gram-negative bacterial pathogen is non-typeable Haemophilus influenzae.

26. The method of claim 24, wherein the endotoxin of the htrB mutant contains a decreased phosphoethanolamine content and an increased hexose content in the mutant endotoxin's inner core, and a pentaacylated or tetraacylated lipid A lacking one or two secondary acyl chains compared to the corresponding wild-type non-typeable Haemophilus influenzae hexaacylated endotoxin.